BAC介导人Paraoxonase基因簇转基因鼠系的建立及其对动脉粥样硬化的影响
摘要
目的:研究Paraoxoanse(PON)基因簇对小鼠动脉粥样硬化的作用及其机制
背景:动脉粥样硬化(AS)及其并发症严重危害人类健康。氧化性低密度脂蛋白(OxLDL)是重要的致AS因子,不但促进AS的发生和发展,还促进AS斑块的破裂。AS斑块破裂是AS并发症及致死致残的重要原因。OxLDL对整个动脉壁都有致AS作用,也可促使巨噬细胞成为斑块的成分和炎症中心。PON在基因组中以基因簇的形式存在,单个PON1、PON2和PON3转基因通过抑制OxLDL的作用而抑制AS。但是整个PON基因簇对AS尤其是斑块稳定性的作用还不明确。
材料和方法:研究建立了人PON基因簇的转基因C57BL/6J小鼠,杂交到Apo E纯合缺失背景,并以高脂饮食分别喂食10周或16周诱导AS的发生。诱导结束后首先检测并比较转基因组和野生对照组的体重、血脂、血压等系统因素,之后处死两组小鼠取其完整动脉进行油红0染色并以Image Pro软件进行双盲定量比较两组小鼠AS发生程度。同时取两组小鼠的心脏以主动脉瓣为标记进行石蜡切片,HE染色进行组织学分析,免疫组化标记主动脉根部斑块的平滑肌细胞和巨噬细胞,并以免疫组化原位检测斑块内MMP-9的表达,比较分析两组斑块在稳定性方面的组织学差别。取两组小鼠的血清以Elisa检测ICAM-1及MCP-Ⅰ。同时在细胞水平,取两组小鼠的腹腔原代巨噬细胞进行氧化应激、炎症、泡沫细胞形成检测。
结果:本研究共建立5株不同拷贝数的转基因小鼠,转入的三个基因家族成员的组织表达谱与小鼠内源性PON一致。PON基因簇转基因鼠无明显异常,体重、血脂、血糖也无异常。选择高拷贝的第二株转基因小鼠进行动脉粥样硬化诱导实验。经过10周诱导,发现雌性和雄性转基因组AS形成程度分别比对照组减少23.5%和33.9%,而其体重、血脂、血糖等系统因素没有明显差异。经过16周诱导,在体重、血脂、血压等系统因素无明显差异的同时,雌性和雄性转基因组AS程度分别比对照组减少33.3%和27.7%,组织学分析发现对照组小鼠的斑块内不但平滑肌增殖和巨噬细胞浸润程度明显比转基因组小鼠严重,而且MMP-9的丰度显著高于转基因组,结合HE染色显示示的转基因组斑块中纤维帽较厚、脂核较小及炎性细胞浸润较少的特点,提示的高脂诱导的AS斑块在转基因组中更具稳定性。同时发现转基因组HDL较对照组能更显著地抑制LDL的氧化。而且高脂诱导AS后,转基因组小鼠的血浆MCP-Ⅰ和ICAM-1水平明显低于对照组。比较两组小鼠腹腔原代巨噬细胞对OxLDL刺激的反应,发现PON基因簇的表达可以抑制刺激导致的氧化应激、炎症、泡沫细胞形成及MMP-9的表达。
结论:PON基因簇不但可以抑制血清oxLDL及其导致的炎症反应,而且可以抑制OxLDL诱导的巨噬细胞促AS反应。从而抑制动脉粥样硬化的发生发展,并稳定斑块。因此,提高PON基因簇的表达和活性可能成为防治动脉粥样硬化的有用手段。
Targets-Elucidtion functions and corresponding mechanisms of Paraoxoanse (PON) gene cluster on atherosclerosis(AS) in mice.
Background- Oxidized LDL(OxLDL) plays very important roles in AS,which not only initiates and ptomotes AS,but also sitmulates the AS plaque to go to rupture.Rupture of AS plaque is the main cause of death resulted from AS. OxLDL induces AS via acting on the whole aorta,it can also promote the macrophages to become components of plaque and center of inflammation.PON exists as a gene cluster in the genome and its member PON1,PON2 and PON3 had been testified being able to inhibit atherogenesis by acting on oxLDL.But effects of the whole cluster on AS,expecially on plaque stability,still remain to be elucidated.
Methods - PON cluster transgenic(PC Tg) mice on C57BL/6J background were generated,crossed to apoE KO background,and induced AS with high fat diet for 10 weeks or 16 weeks.After induction,body weight,serum lipid and sugar indexes and blood pressure were detected and compared the transgenic and wild-type mice.Then we sacrificed these mice,took out the intact aortas and detected the lesion area of the whole aortas with Oil Red O staining.The lesion areas were quilified with Image Pro software and compared the two groups.At the same time,hearts of the two proups were collected and sectioned at the level of aortic root for further histologic analysis.We analyzed these sections morphologically using HE staining,marked smooth muscle cells and macrophages using immunohistochemistry,detected expression of MMP-9 in situ in the sections using immunohistochemistry,and compared these data between two groups in the aspect of plaque stability.Levels of serum ICAM-1 and MCP-Ⅰwere detected using Elisa.ROS generation assay,inflammation detection and foam cell formation experiments were carried out to explore corresponding mechanisms in the MPMs from transgenic mice and wilt-type mice.
Results- Five independent PC Tg mouse lines on C57BL/6J background were generated.Expression pattern of transgenic human PONs was the same with intrinsic mouse PONs.No obvious abnormality characters including body weight, serum lipid and sugar indexes were boserved in the transgenic mice.P2 strain transgenic mice were selected to establish AS models.After 10 weeks of induction,lesion area of transgenic mice aorta decreased 23.5%and 33.9 %compared to control in female and male groups,respectively,while the body weight and high level of serum cholesterol indexes were similar in the two groups.After 16 weeks of induction,lesion area of transgenic mice aorta decreased 33.3%and 27.7%%compared to control in female and male groups, respectively,with the similar body weight and high level of serum cholesterol indexes.Histological analysis revealed that formed plaque in PC TG mice exhibited thicker fibro cap,smaller necrotic core and less infiltration of inflammation cell,thus suggesting that formed plaque intransgenic mice were more stable prone.These results were further convinced by phenomenon of less proliferation of vascular smooth muscle cells,less infiltration of macrophages and lower levels MMP-9 expression in PC TG mice.PC transgene enhanced the ability of HDL to protect LDL against oxidation and inhibited serum level of MCP-Ⅰand ICAM-1.Pro-atherogenic reaction of mice peritoneal macrophages(MPM) induced by oxLDL were significantly inhibited by PC TG as indicated by less ROS generation,inflammation,MMP-9 expression and foam cell formation.
Conclusion- Human PON cluster transgene repressed and stabilized atherosclerosis plaque in vivo via acting not only on serum oxidized LDL but also on vascular macrophage cell.PONs may become useful targets for AS treatment.
背景:动脉粥样硬化(AS)及其并发症严重危害人类健康。氧化性低密度脂蛋白(OxLDL)是重要的致AS因子,不但促进AS的发生和发展,还促进AS斑块的破裂。AS斑块破裂是AS并发症及致死致残的重要原因。OxLDL对整个动脉壁都有致AS作用,也可促使巨噬细胞成为斑块的成分和炎症中心。PON在基因组中以基因簇的形式存在,单个PON1、PON2和PON3转基因通过抑制OxLDL的作用而抑制AS。但是整个PON基因簇对AS尤其是斑块稳定性的作用还不明确。
材料和方法:研究建立了人PON基因簇的转基因C57BL/6J小鼠,杂交到Apo E纯合缺失背景,并以高脂饮食分别喂食10周或16周诱导AS的发生。诱导结束后首先检测并比较转基因组和野生对照组的体重、血脂、血压等系统因素,之后处死两组小鼠取其完整动脉进行油红0染色并以Image Pro软件进行双盲定量比较两组小鼠AS发生程度。同时取两组小鼠的心脏以主动脉瓣为标记进行石蜡切片,HE染色进行组织学分析,免疫组化标记主动脉根部斑块的平滑肌细胞和巨噬细胞,并以免疫组化原位检测斑块内MMP-9的表达,比较分析两组斑块在稳定性方面的组织学差别。取两组小鼠的血清以Elisa检测ICAM-1及MCP-Ⅰ。同时在细胞水平,取两组小鼠的腹腔原代巨噬细胞进行氧化应激、炎症、泡沫细胞形成检测。
结果:本研究共建立5株不同拷贝数的转基因小鼠,转入的三个基因家族成员的组织表达谱与小鼠内源性PON一致。PON基因簇转基因鼠无明显异常,体重、血脂、血糖也无异常。选择高拷贝的第二株转基因小鼠进行动脉粥样硬化诱导实验。经过10周诱导,发现雌性和雄性转基因组AS形成程度分别比对照组减少23.5%和33.9%,而其体重、血脂、血糖等系统因素没有明显差异。经过16周诱导,在体重、血脂、血压等系统因素无明显差异的同时,雌性和雄性转基因组AS程度分别比对照组减少33.3%和27.7%,组织学分析发现对照组小鼠的斑块内不但平滑肌增殖和巨噬细胞浸润程度明显比转基因组小鼠严重,而且MMP-9的丰度显著高于转基因组,结合HE染色显示示的转基因组斑块中纤维帽较厚、脂核较小及炎性细胞浸润较少的特点,提示的高脂诱导的AS斑块在转基因组中更具稳定性。同时发现转基因组HDL较对照组能更显著地抑制LDL的氧化。而且高脂诱导AS后,转基因组小鼠的血浆MCP-Ⅰ和ICAM-1水平明显低于对照组。比较两组小鼠腹腔原代巨噬细胞对OxLDL刺激的反应,发现PON基因簇的表达可以抑制刺激导致的氧化应激、炎症、泡沫细胞形成及MMP-9的表达。
结论:PON基因簇不但可以抑制血清oxLDL及其导致的炎症反应,而且可以抑制OxLDL诱导的巨噬细胞促AS反应。从而抑制动脉粥样硬化的发生发展,并稳定斑块。因此,提高PON基因簇的表达和活性可能成为防治动脉粥样硬化的有用手段。
Targets-Elucidtion functions and corresponding mechanisms of Paraoxoanse (PON) gene cluster on atherosclerosis(AS) in mice.
Background- Oxidized LDL(OxLDL) plays very important roles in AS,which not only initiates and ptomotes AS,but also sitmulates the AS plaque to go to rupture.Rupture of AS plaque is the main cause of death resulted from AS. OxLDL induces AS via acting on the whole aorta,it can also promote the macrophages to become components of plaque and center of inflammation.PON exists as a gene cluster in the genome and its member PON1,PON2 and PON3 had been testified being able to inhibit atherogenesis by acting on oxLDL.But effects of the whole cluster on AS,expecially on plaque stability,still remain to be elucidated.
Methods - PON cluster transgenic(PC Tg) mice on C57BL/6J background were generated,crossed to apoE KO background,and induced AS with high fat diet for 10 weeks or 16 weeks.After induction,body weight,serum lipid and sugar indexes and blood pressure were detected and compared the transgenic and wild-type mice.Then we sacrificed these mice,took out the intact aortas and detected the lesion area of the whole aortas with Oil Red O staining.The lesion areas were quilified with Image Pro software and compared the two groups.At the same time,hearts of the two proups were collected and sectioned at the level of aortic root for further histologic analysis.We analyzed these sections morphologically using HE staining,marked smooth muscle cells and macrophages using immunohistochemistry,detected expression of MMP-9 in situ in the sections using immunohistochemistry,and compared these data between two groups in the aspect of plaque stability.Levels of serum ICAM-1 and MCP-Ⅰwere detected using Elisa.ROS generation assay,inflammation detection and foam cell formation experiments were carried out to explore corresponding mechanisms in the MPMs from transgenic mice and wilt-type mice.
Results- Five independent PC Tg mouse lines on C57BL/6J background were generated.Expression pattern of transgenic human PONs was the same with intrinsic mouse PONs.No obvious abnormality characters including body weight, serum lipid and sugar indexes were boserved in the transgenic mice.P2 strain transgenic mice were selected to establish AS models.After 10 weeks of induction,lesion area of transgenic mice aorta decreased 23.5%and 33.9 %compared to control in female and male groups,respectively,while the body weight and high level of serum cholesterol indexes were similar in the two groups.After 16 weeks of induction,lesion area of transgenic mice aorta decreased 33.3%and 27.7%%compared to control in female and male groups, respectively,with the similar body weight and high level of serum cholesterol indexes.Histological analysis revealed that formed plaque in PC TG mice exhibited thicker fibro cap,smaller necrotic core and less infiltration of inflammation cell,thus suggesting that formed plaque intransgenic mice were more stable prone.These results were further convinced by phenomenon of less proliferation of vascular smooth muscle cells,less infiltration of macrophages and lower levels MMP-9 expression in PC TG mice.PC transgene enhanced the ability of HDL to protect LDL against oxidation and inhibited serum level of MCP-Ⅰand ICAM-1.Pro-atherogenic reaction of mice peritoneal macrophages(MPM) induced by oxLDL were significantly inhibited by PC TG as indicated by less ROS generation,inflammation,MMP-9 expression and foam cell formation.
Conclusion- Human PON cluster transgene repressed and stabilized atherosclerosis plaque in vivo via acting not only on serum oxidized LDL but also on vascular macrophage cell.PONs may become useful targets for AS treatment.
引文
Alexander, R. W. (2002). Oxidized LDL autoantibodies, endothelial dysfunction, and transplant-associated arteriosclerosis. Arterioscler Thromb Vasc Biol 22, 1950-1951.
Argmann, C. A., Sawyez, C. G., Li, S., Nong, Z., Hegele, R. A., Pickering, J. G., and Huff, M. W. (2004).Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins. Arterioscler Thromb Vasc Biol 24, 1290-1296.
Aviram, M., and Rosenblat, M. (2004). Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37, 1304-1316.
Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., 3rd, Tracy, R. E., and Wattigney, W. A. (1998).Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338, 1650-1656.
Berliner, J. (2002). Introduction. Lipid oxidation products and atherosclerosis. Vascul Pharmacol 38,187-191.
Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A., and Witztum, J. L. (2002).Innate and acquired immunity in atherogenesis. Nat Med 8, 1218-1226.
Bochaton-Piallat, M. L., and Gabbiani, G. (2005). Modulation of smooth muscle cell proliferation and migration: role of smooth muscle cell heterogeneity. Handb Exp Pharmacol, 645-663.
Boyle, J. J. (2005). Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol 3, 63-68.
Braunwald, E. (1997). Shattuck lecture—cardiovascular medicine at the turn of the millennium: triumphs,concerns, and opportunities. N Engl J Med 337, 1360-1369.
Choy, J. C., Granville, D. J., Hunt, D. W., and McManus, B. M. (2001). Endothelial cell apoptosis:biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 33, 1673-1690.
Colles, S. M., Maxson, J. M., Carlson, S. G., and Chisolm, G. M. (2001). Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11, 131-138.
Dimmeler, S., Haendeler, J., and Zeiher, A. M. (2002). Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13, 531-536.
Dong, Z. M., Chapman, S. M, Brown, A. A., Frenette, P. S., Hynes, R. O., and Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102, 145-152.
Draganov, D. I., Stetson, P. L., Watson, C. E., Billecke, S. S., and La Du, B. N. (2000). Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 275, 33435-33442.
Dwivedi, A., Anggard, E. E., and Carrier, M. J. (2001). Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB. Biochem Biophys Res Commun 284, 239-244.
Glass, C. K., and Witztum, J. L. (2001). Atherosclerosis. the road ahead. Cell 104, 503-516.
Goligorsky, M. S. (2005). Endothelial cell dysfunction: can't live with it, how to live without it. Am J Physiol Renal Physiol 288, F871-880.
Hansson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352,1685-1695.
Harel, M., Aharoni, A., Gaidukov, L., Brumshtein, B., Khersonsky, O., Meged, R., Dvir, H., Ravelli, R. B.,McCarthy, A., Toker, L., et al. (2004). Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11, 412-419.
Hedrick, C. C., Hassan, K., Hough, G. P., Yoo, J. H., Simzar, S., Quinto, C. R., Kim, S. M., Dooley, A.,Langi, S., Hama, S. Y., et at. (2000). Short-term feeding of atherogenic diet to mice results in reduction of HDL and paraoxonase that may be mediated by an immune mechanism. Arterioscler Thromb Vasc Biol 20,1946-1952.
Hegele, R. A., Connelly, P. W., Scherer, S. W., Hanley, A. J., Harris, S. B., Tsui, L. C., and Zinman, B.(1997). Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82, 3373-3377.
Itabe, H. (2003). Oxidized low-density lipoproteins: what is understood and what remains to be clarified.Biol Pharm Bull 26, 1-9.
Khan, M., Pelengaris, S., Cooper, M., Smith, C., Evan, G., and Betteridge, J. (2003). Oxidised lipoproteins may promote inflammation through the selective delay of engulfment but not binding of apoptotic cells by macrophages. Atherosclerosis 171, 21-29.
Ko, Y. L., Ko, Y. S., Wang, S. M., Hsu, L. A., Chang, C. J., Chu, P. H., Cheng, N. J., Chen, W. J., Chiang, C.W., and Lee, Y. S. (1998). The GIn-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141, 259-264.
Kume, N., and Kita, T. (2001). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in atherogenesis. Trends Cardiovasc Med 11, 22-25.
Leus, F. R., Zwart, M., Kastelein, J. J., and Voorbij, H. A. (2001). PON2 gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients. Atherosclerosis 154, 641-649.
Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874.
Lusis, A. J. (2000). Atherosclerosis. Nature 407, 233-241.
Mackness, M. I., Mackness, B., and Durrington, P. N. (2002). Paraoxonase and coronary heart disease.Atheroscler Suppl 3, 49-55.
Mackness, M. I., Mackness, B., Durrington, P. N., Fogelman, A. M., Berliner, J., Lusis, A. J., Navab, M.,Shih, D., and Fonarow, G. C. (1998). Paraoxonase and coronary heart disease. Curr Opin Lipidol 9, 319-324.
Majesky, M. W. (2002). Mouse model for atherosclerotic plaque rupture. Circulation 105, 2010-2011.
Martinet, W., and Kockx, M. M. (2001). Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr Opin Lipidol 12, 535-541.
Mertens, A., and Holvoet, P. (2001). Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J 15,2073-2084.
Navab, M., Berliner, J. A., Watson, A. D., Hama, S. Y., Territo, M. C, Lusis, A. J., Shih, D. M., Van Lenten,B. J., Frank, J. S., Demer, L. L., et al. (1996). The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 76,831-842.
Ng, C. J., Bourquard, N., Grijalva, V., Hama, S., Shih, D. M., Navab, M., Fogelman, A. M., Lusis, A. J.,Young, S., and Reddy, S. T. (2006). Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem 281,29491-29500.
Ng, C. J., Bourquard, N., Hama, S. Y., Shih, D., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S.T. (2007). Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27, 1368-1374.
Ng, C. J., Shih, D. M., Hama, S. Y., Villa, N., Navab, M., and Reddy, S. T. (2005). The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 38, 153-163.
Ng, C. J., Wadleigh, D. J., Gangopadhyay, A., Hama, S., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S. T. (2001). Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276,44444-44449.
Nicholson, A. C, and Hajjar, D. P. (2004). CD36, oxidized LDL and PPAR gamma: pathological interactions in macrophages and atherosclerosis. Vascul Pharmacol 41, 139-146.
Noris, M., Morigi, M., Donadelli, R., Aiello, S., Foppolo, M., Todeschini, M., Orisio, S., Remuzzi, G., and Remuzzi, A. (1995). Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions.Circ Res 76, 536-543.
Palombo, D., Maione, M., Cifiello, B. I., Udini, M., Maggio, D., and Lupo, M. (1999). Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta. J Cardiovasc Surg (Torino) 40, 257-260.
Panini, S. R., and Sinensky, M. S. (2001). Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12,529-533.
Primo-Parmo, S. L., Sorenson, R. C, Teiber, J., and La Du, B. N. (1996). The human serum paraoxonase/arylesterase gene (PON 1) is one member of a multigene family. Genomics 33, 498-507.
Rader, D. J., and Pure, E. (2005). Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell Metab 1, 223-230.
Reddy, S. T., Wadleigh, D. J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M, Lusis, A. J.,Navab, M., and Fogelman, A. M. (2001). Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21, 542-547.
Rimm, E. B., and Stampfer, M. J. (2000). Antioxidants for vascular disease. Med Clin North Am 84,239-249.
Rosenblat, M., Vaya, J., Shih, D., and Aviram, M. (2005). Paraoxonase I (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 179, 69-77.
Ross, R. (1999). Atherosclerosis--an inflammatory disease. N Engl J Med 340, 115-126.
Rothwell, P. M., Villagra, R., Gibson, R., Donders, R. C, and Warlow, C. P. (2000). Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 355, 19-24.
Schwartz, C. J., Valente, A. J., Sprague, E. A., Kelley, J. L., and Nerem, R. M. (1991). The pathogenesis of atherosclerosis: an overview. Clin Cardiol 14,11-16.
Schwartz, S. M., Galis, Z. S., Rosenfeld, M E., and Falk, E. (2007). Plaque rupture in humans and mice.Arterioscler Thromb Vasc Biol 27, 705-713.
Schwenke, D. C., and Carew, T. E. (1989). Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I.Focal increases in arterial LDL concentration precede development of fatty streak lesions. Arteriosclerosis 9,895-907.
Shah, P. K. (2003). Mechanisms of plaque vulnerability and rupture. J Am Coll Cardiol 41, 15S-22S.
Shih, D. M., Gu, L., Xia, Y. R., Navab, M., Li, W. F., Hama, S., Castellani, L. W., Furlong, C. E., Costa, L.G., Fogelman, A. M., and Lusis, A. J. (1998). Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284-287.
Shih, D. M., Xia, Y. R., Wang, X. P., Miller, E., Castellani, L. W., Subbanagounder, G., Cheroutre, H., Faull,K. F., Berliner, J. A., Witztum, J. L., and Lusis, A. J. (2000). Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275, 17527-17535.
Shih, D. M., Xia, Y. R., Wang, X. P., Wang, S. S., Bourquard, N., Fogelman, A. M., Lusis, A. J., and Reddy,S. T. (2007). Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100,1200-1207.
Shireman, P. K., and Pearce, W. H. (1996). Endothelial cell function: biologic and physiologic functions in health and disease. AJR Am J Roentgenol 166, 7-13.
Steinberg, D. (1997). Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272,20963-20966.
Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C, and Witztum, J. L. (1989). Beyond cholesterol.Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924.
Stemme, S., Faber, B., Holm, J., Wiklund, O., Witztum, J. L., and Hansson, G. K. (1995). T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A 92,3893-3897.
Tabas, I. (2000). Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529,164-174.
Tward, A., Xia, Y. R., Wang, X. P., Shi, Y. S., Park, C., Castellani, L. W., Lusis, A. J., and Shih, D. M.(2002). Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 106, 484-490.
van Berkel, T. J., Out, R., Hoekstra, M., Kuiper, J., Biessen, E., and van Eck, M. (2005). Scavenger receptors:friend or foe in atherosclerosis? Curr Opin Lipidol 16, 525-535.
Verhamme, P., Quarck, R., Hao, H., Knaapen, M., Dymarkowski, S., Bernar, H., Van Cleemput, J., Janssens,S., Vermylen, J., Gabbiani, G., et al. (2002). Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs. Cardiovasc Res 56, 135-144.
Vikramadithyan, R. K., Hu, Y., Noh, H. L., Liang, C. P., Hallam, K., Tall, A. R., Ramasamy, R., and Goldberg, I. J. (2005). Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Invest 115, 2434-2443.
Watanabe, T., Pakala, R., Koba, S., Karagiri, T., and Benedict, C. R. (2001). Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation. Circulation 103, 1440-1445.
Watson, A. D., Berliner, J. A., Hama, S. Y., La Du, B. N., Faull, K. F., Fogelman, A. M., and Navab, M.(1995). Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96, 2882-2891.
Watzinger, N., Schmidt, H.. Schumacher, M., Schmidt, R., Eber, B., Fruhwald, F. M., Zweiker, R., Kostner,G. M., and Klein, W. (2002). Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study. Cardiology 98, 116-122.
Yang, C. M., Chien, C. S., Hsiao, L. D., Pan, S. L., Wang, C. C., Chiu, C. T., and Lin, C. C. (2001).Mitogenic effect of oxidized low-density lipoprotein on vascular smooth muscle cells mediated by activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 132, 1531-1541.
Zettler, M. E., Prociuk, M. A., Austria, J. A., Zhong, G., and Pierce, G. N. (2004). Oxidized low-density lipoprotein retards the growth of proliferating cells by inhibiting nuclear translocation of cell cycle proteins.Arterioscler Thromb Vasc Biol 24, 727-732.
Alexander, R. W. (2002). Oxidized LDL autoantibodies, endothelial dysfunction, and transplant-associated arteriosclerosis. Arterioscler Thromb Vasc Biol 22, 1950-1951.
Argmann, C. A., Sawyez, C. G., Li, S., Nong, Z., Hegele, R. A., Pickering, J. G., and Huff, M. W. (2004).Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins. Arterioscler Thromb Vasc Biol 24, 1290-1296.
Aviram, M., Billecke, S., Sorenson, R., Bisgaier, C., Newton, R., Rosenblat, M., Erogul, J., Hsu, C, Dunlop,C, and La Du, B. (1998). Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 18, 1617-1624.
Aviram, M., Hardak, E., Vaya, J., Mahmood, S., Milo, S., Hoffman, A., Billicke, S., Draganov, D., and Rosenblat, M. (2000). Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101, 2510-2517.
Aviram, M., and Rosenblat, M. (2004). Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37, 1304-1316.
Ayub, A., Mackness, M. I., Arrol, S., Mackness, B., Patel, J., and Durrington, P. N. (1999). Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19, 330-335.
Balogh, Z., Seres, I., Harangi, M., Kovacs, P., Kakuk, G., and Paragh, G. (2001). Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates?Diabetes Metab 27, 604-610.
Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., 3rd, Tracy, R. E., and Wattigney, W. A. (1998).Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults.The Bogalusa Heart Study. N Engl J Med 338, 1650-1656.
Berliner, J. (2002). Introduction. Lipid oxidation products and atherosclerosis. Vascul Pharmacol 38,187-191.
Billecke, S., Draganov, D., Counsell, R., Stetson, P., Watson, C., Hsu, C., and La Du, B. N. (2000). Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 25, 1335-1342.
Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A., and Witztum, J. L. (2002).Innate and acquired immunity in atherogenesis. Nat Med 8, 1218-1226.
Bochaton-Piallat, M. L., and Gabbiani, G. (2005). Modulation of smooth muscle cell proliferation and migration: role of smooth muscle cell heterogeneity. Handb Exp Pharmacol, 645-663.
Bochkov, V. N., Kadi, A., Huber, J., Gruber, F., Binder, B. R., and Leitinger, N. (2002). Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 419, 77-81.
Boisvert, W. A., Santiago, R., Curtiss, L. K., and Terkeltaub, R. A. (1998). A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101, 353-363.
Boring, L., Gosling, J., Cleary, M., and Charo, I. F. (1998). Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394, 894-897.
Braunwald, E. (1997). Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs,concerns, and opportunities. N Engl J Med 337, 1360-1369.
Brophy, V. H., Hastings, M. D., Clendenning, J. B., Richter, R. J., Jarvik, G. P., and Furlong, C. E. (2001).Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 11, 77-84.
Choy, J. C., Granville, D. J., Hunt, D. W., and McManus, B. M. (2001). Endothelial cell apoptosis:biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 33, 1673-1690.
Colles, S. M., Maxson, J. M., Carlson, S. G., and Chisolm, G. M. (2001). Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11, 131-138.
Cybulsky, M. I., and Gimbrone, M. A., Jr. (1991). Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251, 788-791.
de Nigris, F., Lerman, L. O., Ignarro, S. W., Sica, G., Lerman, A., Palinski, W., Ignarro, L. J., and Napoli, C.(2003). Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress. Proc Natl Acad Sci U S A 100, 1420-1425.
de Roos, N. M, Schouten, E. G., Scheek, L. M., van Tol, A., and Katan, M. B. (2002). Replacement of dietary saturated fat with trans fat reduces serum paraoxonase activity in healthy men and women.Metabolism 51, 1534-1537.
Deakin, S., Leviev, I., Gomaraschi, M., Calabresi, L., Franceschini, G., and James, R. W. (2002).Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 277,4301-4308.
Deakin, S., Leviev, I., Guernier, S., and James, R. W. (2003). Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol 23, 2083-2089.
Dimmeler, S., Haendeler, J., and Zeiher, A. M. (2002). Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13, 531-536.
Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., and Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102, 145-152.
Draganov, D. I., Stetson, P. L., Watson, C. E., Billecke, S. S., and La Du, B. N. (2000). Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 275, 33435-33442.
Durrington, P. N., Mackness, B., and Mackness, M. I. (2004). Paraoxonase polymorphisms and coronary heart disease. Lancet 364, 579-580; author reply 580.
Durrington, P. N., Mackness, M. I., Bhatnagar, D., Julier, K., Prais, H., Arrol, S., Morgan, J., and Wood, G.N. (1998). Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer,fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia.Atherosclerosis 138, 217-225.
Dwivedi, A., Anggard, E. E., and Carrier, M. J. (2001). Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB. Biochem Biophys Res Commun 284, 239-244.
Forte, T. M., Subbanagounder, G., Berliner, J. A., Blanche, P. J., Clermont, A. O., Jia, Z., Oda, M. N., Krauss,R. M., and Bielicki, J. K. (2002). Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice. J Lipid Res 43, 477-485.
Glass, C. K., and Witztum, J. L. (2001). Atherosclerosis. the road ahead. Cell 104, 503-516.
Goligorsky, M. S. (2005). Endothelial cell dysfunction: can't live with it, how to live without it. Am J Physiol Renal Physiol 288, F871-880.
Gosling, J., Slaymaker, S., Gu, L., Tseng, S., Ziot, C. H., Young, S. G., Rollins, B. J., and Charo, I. F. (1999).MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B.J Clin Invest 103, 773-778.
Gouedard, C, Barouki, R., and Morel, Y. (2004). Induction of the paraoxonase-1 gene expression by resveratrol. Arterioscler Thromb Vasc Biol 24, 2378-2383.
Hansson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352,1685-1695.
Harel, M., Aharoni, A., Gaidukov, L., Brumshtein, B., Khersonsky, O., Meged, R., Dvir, H., Ravelli, R. B.,McCarthy, A., Toker, L., et al. (2004). Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11, 412-419.
Hassett, C, Richter, R. J., Humbert, R., Chapline, C., Crabb, J. W., Omiecinski, C. J., and Furlong, C. E.(1991). Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence. Biochemistry 30, 10141-10149.
Hedrick, C. C, Hassan, K., Hough, G. P., Yoo, J. H., Simzar, S., Quinto, C. R., Kim, S. M., Dooley, A.,Langi, S., Hama, S. Y., et al. (2000). Short-term feeding of atherogenic diet to mice results in reduction of HDL and paraoxonase that may be mediated by an immune mechanism. Arterioscler Thromb Vasc Biol 20,1946-1952.
Hegele, R. A., Connelly, P. W., Scherer, S. W., Hanley, A. J., Harris, S. B., Tsui, L. C., and Zinman, B.(1997). Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82, 3373-3377.
Horkko, S., Binder, C. J., Shaw, P. X., Chang, M. K., Silverman, G., Palinski, W., and Witztum, J. L. (2000).Immunological responses to oxidized LDL. Free Radic Biol Med 28, 1771-1779.
Ishii, H., Tezuka, T., Ishikawa, H., Takada, K., Oida, K., and Horie, S. (2003). Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RARbeta-RXRalpha heterodimers and Sp1 and Sp3 to their binding sequences in the TM promoter. Blood 101, 4765-4774.
Itabe, H. (2003). Oxidized low-density lipoproteins: what is understood and what remains to be clarified.Biol Pharm Bull 26, 1-9.
Jakubowski, H. (2000). Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275, 3957-3962.
James, R. W., Blatter Garin, M. C, Calabresi, L., Miccoli, R., von Eckardstein, A., Tilly-Kiesi, M., Taskinen,M. R., Assmann, G., and Franceschini, G. (1998). Modulated serum activities and concentrations of paraoxonase in high density Iipoprotein deficiency states. Atherosclerosis 139, 77-82.
James, R. W., Leviev, I., and Righetti, A. (2000). Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease. Circulation 101, 2252-2257.
Jarvik, G. P., Tsai, N. T., McKinstry, L. A., Wani, R., Brophy, V. H., Richter, R. J., Schellenberg, G. D.,Heagerty, P. J., Hatsukami, T. S., and Furlong, C. E. (2002). Vitamin C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol 22, 1329-1333.
Khan, M., Pelengaris. S., Cooper, M., Smith, C., Evan, G., and Betteridge, J. (2003). Oxidised lipoproteins may promote inflammation through the selective delay of enguffment but not binding of apoptotic cells by macrophages. Atherosclerosis 171, 21-29.
Ko, Y. L., Ko, Y. S., Wang, S. M., Hsu, L. A., Chang, C. J., Chu, P. H., Cheng, N. J., Chen, W. J., Chiang, C.W., and Lee, Y. S. (1998). The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141, 259-264.
Kronke, G., Bochkov, V. N., Huber, J., Gruber, F., Bluml, S., Furnkranz, A., Kadi, A., Binder, B. R., and Leitinger, N. (2003). Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein. J Biol Chem 278, 51006-51014.
Kume, N., and Kita, T. (2001). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in atherogenesis. Trends Cardiovasc Med 11, 22-25.
Kumon, Y., Suehiro, T., Ikeda, Y., and Hashimoto, K. (2003). Human paraoxonase-1 gene expression by HepG2 cells is downregulated by interleukin-1beta and tumor necrosis factor-alpha, but is upregulated by interleukin-6. Life Sci 73, 2807-2815.
Lee, R. T., and Libby, P. (1997). The unstable atheroma. Arterioscler Thromb Vasc Biol 17, 1859-1867.
Lee, T. S., and Chau, L. Y. (2002). Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8, 240-246.
Leitinger, N., Tyner, T. R., Oslund, L., Rizza, C., Subbanagounder, G., Lee, H., Shih, P. T., Mackman, N.,Tigyi, G., Territo, M. C, et al. (1999). Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc Natl Acad Sci U S A 96, 12010-12015.
Leus, F. R., Zwart, M., Kastelein, J. J., and Voorbij, H. A. (2001). PON2 gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients. Atherosclerosis 154, 641-649.
Leviev, I., and James, R. W. (2000). Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol 20, 516-521.
Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874.
Lusis, A. J. (2000). Atherosclerosis. Nature 407, 233-241.
Mackness, B., Durrington, P., McEIduff, P., Yarnell, J., Azam, N., Watt, M., and Mackness, M. (2003). Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study. Circulation 107,2775-2779.
Mackness, M. I. (1989). 'A'-esterases. Enzymes looking for a role? Biochem Pharmacol 38, 385-390.
Mackness, M. I., Mackness, B., and Durrington, P. N. (2002). Paraoxonase and coronary heart disease.Atheroscler Suppl 3, 49-55.
Mackness, M. I., Mackness, B., Durrington, P. N., Fogelman, A. M., Berliner, J., Lusis, A. J., Navab, M.,
Shih, D., and Fonarow, G. C. (1998). Paraoxonase and coronary heart disease. Curr Opin Lipidol 9, 319-324.
Majesky, M. W. (2002). Mouse model for atherosclerotic plaque rupture. Circulation 105, 2010-2011.
Malin, R., Jarvinen, O., Sisto, T., Koivula, T., and Lehtimaki, T. (2001). Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis. Atherosclerosis 157,301-307.
Martinet, W., and Kockx, M. M. (2001). Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr Opin Lipidol 12, 535-541.
Mertens, A., and Holvoet, P. (2001). Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J 15,2073-2084.
Muller, K., Carpenter, K. L., and Mitchinson, M. J. (1998). Cell-mediated oxidation of LDL: comparison of different cell types of the atherosclerotic lesion. Free Radic Res 29, 207-220.
Navab, M., Berliner, J. A., Watson, A. D., Hama, S. Y., Territo, M. C., Lusis, A. J., Shih, D. M., Van Lenten,B. J., Frank, J. S., Demer, L. L., et al. (1996). The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 16,831-842.
Navab, M., Hama-Levy, S., Van Lenten, B. J., Fonarow, G. C., Cardinez, C. J., Castellani, L. W., Brennan,M. L., Lusis, A. J., Fogelman, A. M., and La Du, B. N. (1997). Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 99, 2005-2019.
Ng, C. J., Bourquard, N., Grijalva, V., Hama, S., Shih, D. M., Navab, M., Fogelman, A. M., Lusis, A. J.,Young, S., and Reddy, S. T. (2006). Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem 281,29491-29500.
Ng, C. J., Bourquard, N., Hama, S. Y., Shih, D., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S.T. (2007). Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27, 1368-1374.
Ng, C. J., Shih, D. M., Hama, S. Y., Villa, N., Navab, M., and Reddy, S. T. (2005). The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 38, 153-163.
Ng, C. J., Wadleigh, D. J., Gangopadhyay, A., Hama, S., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S. T. (2001). Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276,44444.44449.
Nicholson, A. C., and Hajjar, D. P. (2004). CD36, oxidized LDL and PPAR gamma: pathological interactions in macrophages and atherosclerosis. Vascul Pharmacol 41, 139-146.
Nishio, E., and Watanabe, Y. (1997). Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme's free thiols. Biochem Biophys Res Commun 236, 289-293.
Noris, M., Morigi, M., Donadelli, R., Aiello, S., Foppolo, M., Todeschini, M., Orisio, S., Remuzzi, G., and Remuzzi, A. (1995). Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions.Circ Res 76, 536-543.
Osaki, F., Ikeda, Y., Suehiro, T., Ota, K., Tsuzura, S., Arii, K., Kumon, Y., and Hashimoto, K. (2004). Roles of Sp1 and protein kinase C in regulation of human serum paraoxonase 1 (PON1) gene transcription in HepG2 cells. Atherosclerosis 176, 279-287.
Palombo, D., Maione, M., Cifiello, B. I., Udini, M., Maggio, D., and Lupo, M. (1999). Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta. J Cardiovasc Surg(Torino) 40, 257-260.
Panini, S. R., and Sinensky, M. S. (2001). Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12,529-533.
Prager, G. W., and Binder, B. R. (2004). Genetic determinants: is there an "atherosclerosis gene"? Acta Med Austriaca 31, 1-7.
Primo-Parmo, S. L., Sorenson, R. C, Teiber, J., and La Du, B. N. (1996). The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 33, 498-507.
Rader, D. J., and Pure, E. (2005). Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell Metab 1, 223-230.
Rainwater, D. L., Mahaney, M. C., Wang, X. L., Rogers, J., Cox, L. A., and Vandeberg, J. L. (2005).Determinants of variation in serum paraoxonase enzyme activity in baboons. J Lipid Res 46, 1450-1456.
Reddy, S. T., Wadleigh. D. J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M., Lusis, A. J.,Navab, M., and Fogelman, A. M. (2001). Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21, 542-547.
Richter, R. J., and Furlong, C. E. (1999). Determination of paraoxonase (PONI) status requires more than genotyping. Pharmacogenetics 9, 745-753.
Rimm, E. B., and Stampfer, M. J. (2000). Antioxidants for vascular disease. Med Clin North Am 84,239-249.
Rosenblat, M., Draganov, D., Watson, C. E., Bisgaier, C. L., La Du, B. N., and Aviram, M. (2003). Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler Thromb Vasc Biol 23, 468-474.
Rosenblat, M., Hayek, T., Hussein, K., and Aviram, M. (2004). Decreased macrophage paraoxonase 2 expression in patients with hypercholesterolemia is the result of their increased cellular cholesterol content:effect of atorvastatin therapy. Arterioscler Thromb Vasc Biol 24, 175-180.
Rosenblat, M., Vaya, J., Shih, D., and Aviram, M. (2005). Paraoxonase 1 (PON 1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 179, 69-77.
Ross, R. (1999). Atherosclerosis--an inflammatory disease. N Engl J Med 340, 115-126.
Rothwell, P. M., Villagra, R., Gibson, R., Donders, R. C., and Warlow, C. P. (2000). Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 355, 19-24.
Schug, J., and Overton, G. C. (1997). Modeling transcription factor binding sites with Gibbs Sampling and Minimum Description Length encoding. Proc Int Conf Intell Syst Mol Biol 5, 268-271.
Schwartz, C. J., Valente, A. J., Sprague, E. A., Kelley, J. L., and Nerem, R. M. (1991). The pathogenesis of atherosclerosis: an overview. Clin Cardiol 14,11-16.
Schwartz, S. M., Galis, Z. S., Rosenfeld, M. E., and Falk, E. (2007). Plaque rupture in humans and mice.Arterioscler Thromb Vasc Biol 27, 705-713.
Schwenke, D. C., and Carew, T. E. (1989). Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I.Focal increases in arterial LDL concentration precede development of fatty streak lesions. Arteriosclerosis 9,895-907.
Shih, D. M., Gu, L., Xia, Y. R., Navab, M., Li, W. F., Hama, S., Castellani, L. W., Furlong, C. E., Costa, L.G., Fogelman, A. M., and Lusis, A. J. (1998). Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284-287.
Shih, D. M., Xia, Y. R., Wang, X. P., Miller, E., Castellani, L. W., Subbanagounder, G., Cheroutre, H., Faull,K. F., Berliner, J. A., Witztum, J. L., and Lusis, A. J. (2000). Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275, 17527-17535.
Shih, D. M., Xia, Y. R., Wang, X. P., Wang, S. S., Bourquard, N., Fogelman, A. M., Lusis, A. J., and Reddy,S. T. (2007). Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100,1200-1207.
Shireman, P. K., and Pearce, W. H. (1996). Endothelial cell function: biologic and physiologic functions in health and disease. AJR Am J Roentgenol 166, 7-13.
Sorenson, R. C, Bisgaier, C. L., Aviram, M., Hsu, C., Billecke, S., and La Du, B. N. (1999). Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids : apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 19, 2214-2225.
Steinberg, D. (1997). Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272, 20963-20966.
Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C., and Witztum, J. L. (1989). Beyond cholesterol.Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924.
Stemme, S., Faber, B., Holm, J., Wiklund, O., Witztum, J. L., and Hansson, G. K. (1995). T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A 92,3893-3897.
Tabas, I. (2000). Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529,164-174.
Teiber, J. F., Draganov, D. I., and La Du, B. N. (2003). Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Biochem Pharmacol 66, 887-896.
Tomas, M., Senti, M., Elosua, R., Vila, J., Sala, J., Masia, R., and Marrugat, J. (2001). Interaction between the Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high-density lipoprotein cholesterol and paraoxonase activity. Eur J Pharmacol 432, 121-128.
Tsimihodimos, V., Karabina, S. A., Tambaki, A. P., Bairaktari, E., Goudevenos, J. A., Chapman, M. J.,Elisaf, M., and Tselepis, A. D. (2002). Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type 1IA and type IIB. Arterioscler Thromb Vasc Biol 22,306-311.
Tward, A., Xia, Y. R., Wang, X. P., Shi, Y. S., Park, C., Castellani, L. W., Lusis, A. J., and Shih, D. M.(2002). Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 106, 484-490.
van Berkel, T. J., Out, R., Hoekstra, M., Kuiper, J., Biessen, E., and van Eck, M. (2005). Scavenger receptors:friend or foe in atherosclerosis? Curr Opin Lipidol 16, 525-535.
van der Gaag, M. S., van Tol, A., Scheek, L. ML, James, R. W., Urgert, R., Schaafsma, G., and Hendriks, H.F. (1999). Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men. Atherosclerosis 147,405-410.
Van Lenten, B. J., Wagner, A. C., Navab, M., and Fogelman, A. M. (2001). Oxidized phospholipids induce changes in hepatic paraoxonase and ApoJ but not monocyte chemoattractant protein-1 via interleukin-6. J Biol Chem 276, 1923-1929.
Verhamme, P., Quarck, R., Hao, H., Knaapen, M., Dymarkowski, S., Bernar, H., Van Cleemput, J., Janssens,S., Vermylen, J., Gabbiani, G., et al. (2002). Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs. Cardiovasc Res 56, 135-144.
Wallace, A. J., Sutherland, W. H., Mann, J. I., and Williams, S. M. (2001). The effect of meals rich in thermally stressed olive and safflower oils on postprandial serum paraoxonase activity in patients with diabetes. Eur J Clin Nutr 55, 951 -958.
Watanabe, T., Pakala, R., Koba, S., Katagiri, T., and Benedict, C. R. (2001). Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation. Circulation 103, 1440-1445.
Watson, A. D., Berliner, J. A., Hama, S. Y., La Du, B. N., Faull, K. F., Fogelman, A. M., and Navab, M.(1995). Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96, 2882-2891.
Watzinger, N., Schmidt, H., Schumacher, M., Schmidt, R., Eber, B., Fruhwald, F. M., Zweiker, R., Kostner,G. M., and Klein, W. (2002). Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study. Cardiology 98, 116-122.
Witztum, J. L., and Steinberg, D. (1991). Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88, 1785-1792.
Yamada, Y., Doi, T., Hamakubo, T., and Kodama, T. (1998). Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system. Cell Mol Life Sci 54, 628-640.
Yang, C. M., Chien, C. S., Hsiao, L. D., Pan, S. L., Wang, C. C., Chiu, C. T., and Lin, C. C. (2001).Mitogenic effect of oxidized low-density lipoprotein on vascular smooth muscle cells mediated by activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 132, 1531-1541.
Yusuf, S., Dagenais, G., Pogue, J., Bosch, J., and Sleight, P. (2000). Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.N Engl J Med 342, 154-160.
Zettler, M. E., Prociuk, M. A., Austria, J. A., Zhong, G., and Pierce, G. N. (2004). Oxidized low-density lipoprotein retards the growth of proliferating cells by inhibiting nuclear translocation of cell cycle proteins.Arterioscler Thromb Vasc Biol 24, 727-732.
Argmann, C. A., Sawyez, C. G., Li, S., Nong, Z., Hegele, R. A., Pickering, J. G., and Huff, M. W. (2004).Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins. Arterioscler Thromb Vasc Biol 24, 1290-1296.
Aviram, M., and Rosenblat, M. (2004). Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37, 1304-1316.
Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., 3rd, Tracy, R. E., and Wattigney, W. A. (1998).Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med 338, 1650-1656.
Berliner, J. (2002). Introduction. Lipid oxidation products and atherosclerosis. Vascul Pharmacol 38,187-191.
Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A., and Witztum, J. L. (2002).Innate and acquired immunity in atherogenesis. Nat Med 8, 1218-1226.
Bochaton-Piallat, M. L., and Gabbiani, G. (2005). Modulation of smooth muscle cell proliferation and migration: role of smooth muscle cell heterogeneity. Handb Exp Pharmacol, 645-663.
Boyle, J. J. (2005). Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture. Curr Vasc Pharmacol 3, 63-68.
Braunwald, E. (1997). Shattuck lecture—cardiovascular medicine at the turn of the millennium: triumphs,concerns, and opportunities. N Engl J Med 337, 1360-1369.
Choy, J. C., Granville, D. J., Hunt, D. W., and McManus, B. M. (2001). Endothelial cell apoptosis:biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 33, 1673-1690.
Colles, S. M., Maxson, J. M., Carlson, S. G., and Chisolm, G. M. (2001). Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11, 131-138.
Dimmeler, S., Haendeler, J., and Zeiher, A. M. (2002). Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13, 531-536.
Dong, Z. M., Chapman, S. M, Brown, A. A., Frenette, P. S., Hynes, R. O., and Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102, 145-152.
Draganov, D. I., Stetson, P. L., Watson, C. E., Billecke, S. S., and La Du, B. N. (2000). Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 275, 33435-33442.
Dwivedi, A., Anggard, E. E., and Carrier, M. J. (2001). Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB. Biochem Biophys Res Commun 284, 239-244.
Glass, C. K., and Witztum, J. L. (2001). Atherosclerosis. the road ahead. Cell 104, 503-516.
Goligorsky, M. S. (2005). Endothelial cell dysfunction: can't live with it, how to live without it. Am J Physiol Renal Physiol 288, F871-880.
Hansson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352,1685-1695.
Harel, M., Aharoni, A., Gaidukov, L., Brumshtein, B., Khersonsky, O., Meged, R., Dvir, H., Ravelli, R. B.,McCarthy, A., Toker, L., et al. (2004). Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11, 412-419.
Hedrick, C. C., Hassan, K., Hough, G. P., Yoo, J. H., Simzar, S., Quinto, C. R., Kim, S. M., Dooley, A.,Langi, S., Hama, S. Y., et at. (2000). Short-term feeding of atherogenic diet to mice results in reduction of HDL and paraoxonase that may be mediated by an immune mechanism. Arterioscler Thromb Vasc Biol 20,1946-1952.
Hegele, R. A., Connelly, P. W., Scherer, S. W., Hanley, A. J., Harris, S. B., Tsui, L. C., and Zinman, B.(1997). Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82, 3373-3377.
Itabe, H. (2003). Oxidized low-density lipoproteins: what is understood and what remains to be clarified.Biol Pharm Bull 26, 1-9.
Khan, M., Pelengaris, S., Cooper, M., Smith, C., Evan, G., and Betteridge, J. (2003). Oxidised lipoproteins may promote inflammation through the selective delay of engulfment but not binding of apoptotic cells by macrophages. Atherosclerosis 171, 21-29.
Ko, Y. L., Ko, Y. S., Wang, S. M., Hsu, L. A., Chang, C. J., Chu, P. H., Cheng, N. J., Chen, W. J., Chiang, C.W., and Lee, Y. S. (1998). The GIn-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141, 259-264.
Kume, N., and Kita, T. (2001). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in atherogenesis. Trends Cardiovasc Med 11, 22-25.
Leus, F. R., Zwart, M., Kastelein, J. J., and Voorbij, H. A. (2001). PON2 gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients. Atherosclerosis 154, 641-649.
Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874.
Lusis, A. J. (2000). Atherosclerosis. Nature 407, 233-241.
Mackness, M. I., Mackness, B., and Durrington, P. N. (2002). Paraoxonase and coronary heart disease.Atheroscler Suppl 3, 49-55.
Mackness, M. I., Mackness, B., Durrington, P. N., Fogelman, A. M., Berliner, J., Lusis, A. J., Navab, M.,Shih, D., and Fonarow, G. C. (1998). Paraoxonase and coronary heart disease. Curr Opin Lipidol 9, 319-324.
Majesky, M. W. (2002). Mouse model for atherosclerotic plaque rupture. Circulation 105, 2010-2011.
Martinet, W., and Kockx, M. M. (2001). Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr Opin Lipidol 12, 535-541.
Mertens, A., and Holvoet, P. (2001). Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J 15,2073-2084.
Navab, M., Berliner, J. A., Watson, A. D., Hama, S. Y., Territo, M. C, Lusis, A. J., Shih, D. M., Van Lenten,B. J., Frank, J. S., Demer, L. L., et al. (1996). The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 76,831-842.
Ng, C. J., Bourquard, N., Grijalva, V., Hama, S., Shih, D. M., Navab, M., Fogelman, A. M., Lusis, A. J.,Young, S., and Reddy, S. T. (2006). Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem 281,29491-29500.
Ng, C. J., Bourquard, N., Hama, S. Y., Shih, D., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S.T. (2007). Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27, 1368-1374.
Ng, C. J., Shih, D. M., Hama, S. Y., Villa, N., Navab, M., and Reddy, S. T. (2005). The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 38, 153-163.
Ng, C. J., Wadleigh, D. J., Gangopadhyay, A., Hama, S., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S. T. (2001). Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276,44444-44449.
Nicholson, A. C, and Hajjar, D. P. (2004). CD36, oxidized LDL and PPAR gamma: pathological interactions in macrophages and atherosclerosis. Vascul Pharmacol 41, 139-146.
Noris, M., Morigi, M., Donadelli, R., Aiello, S., Foppolo, M., Todeschini, M., Orisio, S., Remuzzi, G., and Remuzzi, A. (1995). Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions.Circ Res 76, 536-543.
Palombo, D., Maione, M., Cifiello, B. I., Udini, M., Maggio, D., and Lupo, M. (1999). Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta. J Cardiovasc Surg (Torino) 40, 257-260.
Panini, S. R., and Sinensky, M. S. (2001). Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12,529-533.
Primo-Parmo, S. L., Sorenson, R. C, Teiber, J., and La Du, B. N. (1996). The human serum paraoxonase/arylesterase gene (PON 1) is one member of a multigene family. Genomics 33, 498-507.
Rader, D. J., and Pure, E. (2005). Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell Metab 1, 223-230.
Reddy, S. T., Wadleigh, D. J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M, Lusis, A. J.,Navab, M., and Fogelman, A. M. (2001). Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21, 542-547.
Rimm, E. B., and Stampfer, M. J. (2000). Antioxidants for vascular disease. Med Clin North Am 84,239-249.
Rosenblat, M., Vaya, J., Shih, D., and Aviram, M. (2005). Paraoxonase I (PON1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 179, 69-77.
Ross, R. (1999). Atherosclerosis--an inflammatory disease. N Engl J Med 340, 115-126.
Rothwell, P. M., Villagra, R., Gibson, R., Donders, R. C, and Warlow, C. P. (2000). Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 355, 19-24.
Schwartz, C. J., Valente, A. J., Sprague, E. A., Kelley, J. L., and Nerem, R. M. (1991). The pathogenesis of atherosclerosis: an overview. Clin Cardiol 14,11-16.
Schwartz, S. M., Galis, Z. S., Rosenfeld, M E., and Falk, E. (2007). Plaque rupture in humans and mice.Arterioscler Thromb Vasc Biol 27, 705-713.
Schwenke, D. C., and Carew, T. E. (1989). Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I.Focal increases in arterial LDL concentration precede development of fatty streak lesions. Arteriosclerosis 9,895-907.
Shah, P. K. (2003). Mechanisms of plaque vulnerability and rupture. J Am Coll Cardiol 41, 15S-22S.
Shih, D. M., Gu, L., Xia, Y. R., Navab, M., Li, W. F., Hama, S., Castellani, L. W., Furlong, C. E., Costa, L.G., Fogelman, A. M., and Lusis, A. J. (1998). Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284-287.
Shih, D. M., Xia, Y. R., Wang, X. P., Miller, E., Castellani, L. W., Subbanagounder, G., Cheroutre, H., Faull,K. F., Berliner, J. A., Witztum, J. L., and Lusis, A. J. (2000). Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275, 17527-17535.
Shih, D. M., Xia, Y. R., Wang, X. P., Wang, S. S., Bourquard, N., Fogelman, A. M., Lusis, A. J., and Reddy,S. T. (2007). Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100,1200-1207.
Shireman, P. K., and Pearce, W. H. (1996). Endothelial cell function: biologic and physiologic functions in health and disease. AJR Am J Roentgenol 166, 7-13.
Steinberg, D. (1997). Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272,20963-20966.
Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C, and Witztum, J. L. (1989). Beyond cholesterol.Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924.
Stemme, S., Faber, B., Holm, J., Wiklund, O., Witztum, J. L., and Hansson, G. K. (1995). T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A 92,3893-3897.
Tabas, I. (2000). Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529,164-174.
Tward, A., Xia, Y. R., Wang, X. P., Shi, Y. S., Park, C., Castellani, L. W., Lusis, A. J., and Shih, D. M.(2002). Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 106, 484-490.
van Berkel, T. J., Out, R., Hoekstra, M., Kuiper, J., Biessen, E., and van Eck, M. (2005). Scavenger receptors:friend or foe in atherosclerosis? Curr Opin Lipidol 16, 525-535.
Verhamme, P., Quarck, R., Hao, H., Knaapen, M., Dymarkowski, S., Bernar, H., Van Cleemput, J., Janssens,S., Vermylen, J., Gabbiani, G., et al. (2002). Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs. Cardiovasc Res 56, 135-144.
Vikramadithyan, R. K., Hu, Y., Noh, H. L., Liang, C. P., Hallam, K., Tall, A. R., Ramasamy, R., and Goldberg, I. J. (2005). Human aldose reductase expression accelerates diabetic atherosclerosis in transgenic mice. J Clin Invest 115, 2434-2443.
Watanabe, T., Pakala, R., Koba, S., Karagiri, T., and Benedict, C. R. (2001). Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation. Circulation 103, 1440-1445.
Watson, A. D., Berliner, J. A., Hama, S. Y., La Du, B. N., Faull, K. F., Fogelman, A. M., and Navab, M.(1995). Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96, 2882-2891.
Watzinger, N., Schmidt, H.. Schumacher, M., Schmidt, R., Eber, B., Fruhwald, F. M., Zweiker, R., Kostner,G. M., and Klein, W. (2002). Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study. Cardiology 98, 116-122.
Yang, C. M., Chien, C. S., Hsiao, L. D., Pan, S. L., Wang, C. C., Chiu, C. T., and Lin, C. C. (2001).Mitogenic effect of oxidized low-density lipoprotein on vascular smooth muscle cells mediated by activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 132, 1531-1541.
Zettler, M. E., Prociuk, M. A., Austria, J. A., Zhong, G., and Pierce, G. N. (2004). Oxidized low-density lipoprotein retards the growth of proliferating cells by inhibiting nuclear translocation of cell cycle proteins.Arterioscler Thromb Vasc Biol 24, 727-732.
Alexander, R. W. (2002). Oxidized LDL autoantibodies, endothelial dysfunction, and transplant-associated arteriosclerosis. Arterioscler Thromb Vasc Biol 22, 1950-1951.
Argmann, C. A., Sawyez, C. G., Li, S., Nong, Z., Hegele, R. A., Pickering, J. G., and Huff, M. W. (2004).Human smooth muscle cell subpopulations differentially accumulate cholesteryl ester when exposed to native and oxidized lipoproteins. Arterioscler Thromb Vasc Biol 24, 1290-1296.
Aviram, M., Billecke, S., Sorenson, R., Bisgaier, C., Newton, R., Rosenblat, M., Erogul, J., Hsu, C, Dunlop,C, and La Du, B. (1998). Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R. Arterioscler Thromb Vasc Biol 18, 1617-1624.
Aviram, M., Hardak, E., Vaya, J., Mahmood, S., Milo, S., Hoffman, A., Billicke, S., Draganov, D., and Rosenblat, M. (2000). Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions: PON1 esterase and peroxidase-like activities. Circulation 101, 2510-2517.
Aviram, M., and Rosenblat, M. (2004). Paraoxonases 1, 2, and 3, oxidative stress, and macrophage foam cell formation during atherosclerosis development. Free Radic Biol Med 37, 1304-1316.
Ayub, A., Mackness, M. I., Arrol, S., Mackness, B., Patel, J., and Durrington, P. N. (1999). Serum paraoxonase after myocardial infarction. Arterioscler Thromb Vasc Biol 19, 330-335.
Balogh, Z., Seres, I., Harangi, M., Kovacs, P., Kakuk, G., and Paragh, G. (2001). Gemfibrozil increases paraoxonase activity in type 2 diabetic patients. A new hypothesis of the beneficial action of fibrates?Diabetes Metab 27, 604-610.
Berenson, G. S., Srinivasan, S. R., Bao, W., Newman, W. P., 3rd, Tracy, R. E., and Wattigney, W. A. (1998).Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults.The Bogalusa Heart Study. N Engl J Med 338, 1650-1656.
Berliner, J. (2002). Introduction. Lipid oxidation products and atherosclerosis. Vascul Pharmacol 38,187-191.
Billecke, S., Draganov, D., Counsell, R., Stetson, P., Watson, C., Hsu, C., and La Du, B. N. (2000). Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters. Drug Metab Dispos 25, 1335-1342.
Binder, C. J., Chang, M. K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A., and Witztum, J. L. (2002).Innate and acquired immunity in atherogenesis. Nat Med 8, 1218-1226.
Bochaton-Piallat, M. L., and Gabbiani, G. (2005). Modulation of smooth muscle cell proliferation and migration: role of smooth muscle cell heterogeneity. Handb Exp Pharmacol, 645-663.
Bochkov, V. N., Kadi, A., Huber, J., Gruber, F., Binder, B. R., and Leitinger, N. (2002). Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 419, 77-81.
Boisvert, W. A., Santiago, R., Curtiss, L. K., and Terkeltaub, R. A. (1998). A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 101, 353-363.
Boring, L., Gosling, J., Cleary, M., and Charo, I. F. (1998). Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394, 894-897.
Braunwald, E. (1997). Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs,concerns, and opportunities. N Engl J Med 337, 1360-1369.
Brophy, V. H., Hastings, M. D., Clendenning, J. B., Richter, R. J., Jarvik, G. P., and Furlong, C. E. (2001).Polymorphisms in the human paraoxonase (PON1) promoter. Pharmacogenetics 11, 77-84.
Choy, J. C., Granville, D. J., Hunt, D. W., and McManus, B. M. (2001). Endothelial cell apoptosis:biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 33, 1673-1690.
Colles, S. M., Maxson, J. M., Carlson, S. G., and Chisolm, G. M. (2001). Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11, 131-138.
Cybulsky, M. I., and Gimbrone, M. A., Jr. (1991). Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science 251, 788-791.
de Nigris, F., Lerman, L. O., Ignarro, S. W., Sica, G., Lerman, A., Palinski, W., Ignarro, L. J., and Napoli, C.(2003). Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress. Proc Natl Acad Sci U S A 100, 1420-1425.
de Roos, N. M, Schouten, E. G., Scheek, L. M., van Tol, A., and Katan, M. B. (2002). Replacement of dietary saturated fat with trans fat reduces serum paraoxonase activity in healthy men and women.Metabolism 51, 1534-1537.
Deakin, S., Leviev, I., Gomaraschi, M., Calabresi, L., Franceschini, G., and James, R. W. (2002).Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 277,4301-4308.
Deakin, S., Leviev, I., Guernier, S., and James, R. W. (2003). Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol 23, 2083-2089.
Dimmeler, S., Haendeler, J., and Zeiher, A. M. (2002). Regulation of endothelial cell apoptosis in atherothrombosis. Curr Opin Lipidol 13, 531-536.
Dong, Z. M., Chapman, S. M., Brown, A. A., Frenette, P. S., Hynes, R. O., and Wagner, D. D. (1998). The combined role of P- and E-selectins in atherosclerosis. J Clin Invest 102, 145-152.
Draganov, D. I., Stetson, P. L., Watson, C. E., Billecke, S. S., and La Du, B. N. (2000). Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem 275, 33435-33442.
Durrington, P. N., Mackness, B., and Mackness, M. I. (2004). Paraoxonase polymorphisms and coronary heart disease. Lancet 364, 579-580; author reply 580.
Durrington, P. N., Mackness, M. I., Bhatnagar, D., Julier, K., Prais, H., Arrol, S., Morgan, J., and Wood, G.N. (1998). Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer,fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia.Atherosclerosis 138, 217-225.
Dwivedi, A., Anggard, E. E., and Carrier, M. J. (2001). Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB. Biochem Biophys Res Commun 284, 239-244.
Forte, T. M., Subbanagounder, G., Berliner, J. A., Blanche, P. J., Clermont, A. O., Jia, Z., Oda, M. N., Krauss,R. M., and Bielicki, J. K. (2002). Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice. J Lipid Res 43, 477-485.
Glass, C. K., and Witztum, J. L. (2001). Atherosclerosis. the road ahead. Cell 104, 503-516.
Goligorsky, M. S. (2005). Endothelial cell dysfunction: can't live with it, how to live without it. Am J Physiol Renal Physiol 288, F871-880.
Gosling, J., Slaymaker, S., Gu, L., Tseng, S., Ziot, C. H., Young, S. G., Rollins, B. J., and Charo, I. F. (1999).MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B.J Clin Invest 103, 773-778.
Gouedard, C, Barouki, R., and Morel, Y. (2004). Induction of the paraoxonase-1 gene expression by resveratrol. Arterioscler Thromb Vasc Biol 24, 2378-2383.
Hansson, G. K. (2005). Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352,1685-1695.
Harel, M., Aharoni, A., Gaidukov, L., Brumshtein, B., Khersonsky, O., Meged, R., Dvir, H., Ravelli, R. B.,McCarthy, A., Toker, L., et al. (2004). Structure and evolution of the serum paraoxonase family of detoxifying and anti-atherosclerotic enzymes. Nat Struct Mol Biol 11, 412-419.
Hassett, C, Richter, R. J., Humbert, R., Chapline, C., Crabb, J. W., Omiecinski, C. J., and Furlong, C. E.(1991). Characterization of cDNA clones encoding rabbit and human serum paraoxonase: the mature protein retains its signal sequence. Biochemistry 30, 10141-10149.
Hedrick, C. C, Hassan, K., Hough, G. P., Yoo, J. H., Simzar, S., Quinto, C. R., Kim, S. M., Dooley, A.,Langi, S., Hama, S. Y., et al. (2000). Short-term feeding of atherogenic diet to mice results in reduction of HDL and paraoxonase that may be mediated by an immune mechanism. Arterioscler Thromb Vasc Biol 20,1946-1952.
Hegele, R. A., Connelly, P. W., Scherer, S. W., Hanley, A. J., Harris, S. B., Tsui, L. C., and Zinman, B.(1997). Paraoxonase-2 gene (PON2) G148 variant associated with elevated fasting plasma glucose in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 82, 3373-3377.
Horkko, S., Binder, C. J., Shaw, P. X., Chang, M. K., Silverman, G., Palinski, W., and Witztum, J. L. (2000).Immunological responses to oxidized LDL. Free Radic Biol Med 28, 1771-1779.
Ishii, H., Tezuka, T., Ishikawa, H., Takada, K., Oida, K., and Horie, S. (2003). Oxidized phospholipids in oxidized low-density lipoprotein down-regulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RARbeta-RXRalpha heterodimers and Sp1 and Sp3 to their binding sequences in the TM promoter. Blood 101, 4765-4774.
Itabe, H. (2003). Oxidized low-density lipoproteins: what is understood and what remains to be clarified.Biol Pharm Bull 26, 1-9.
Jakubowski, H. (2000). Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275, 3957-3962.
James, R. W., Blatter Garin, M. C, Calabresi, L., Miccoli, R., von Eckardstein, A., Tilly-Kiesi, M., Taskinen,M. R., Assmann, G., and Franceschini, G. (1998). Modulated serum activities and concentrations of paraoxonase in high density Iipoprotein deficiency states. Atherosclerosis 139, 77-82.
James, R. W., Leviev, I., and Righetti, A. (2000). Smoking is associated with reduced serum paraoxonase activity and concentration in patients with coronary artery disease. Circulation 101, 2252-2257.
Jarvik, G. P., Tsai, N. T., McKinstry, L. A., Wani, R., Brophy, V. H., Richter, R. J., Schellenberg, G. D.,Heagerty, P. J., Hatsukami, T. S., and Furlong, C. E. (2002). Vitamin C and E intake is associated with increased paraoxonase activity. Arterioscler Thromb Vasc Biol 22, 1329-1333.
Khan, M., Pelengaris. S., Cooper, M., Smith, C., Evan, G., and Betteridge, J. (2003). Oxidised lipoproteins may promote inflammation through the selective delay of enguffment but not binding of apoptotic cells by macrophages. Atherosclerosis 171, 21-29.
Ko, Y. L., Ko, Y. S., Wang, S. M., Hsu, L. A., Chang, C. J., Chu, P. H., Cheng, N. J., Chen, W. J., Chiang, C.W., and Lee, Y. S. (1998). The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141, 259-264.
Kronke, G., Bochkov, V. N., Huber, J., Gruber, F., Bluml, S., Furnkranz, A., Kadi, A., Binder, B. R., and Leitinger, N. (2003). Oxidized phospholipids induce expression of human heme oxygenase-1 involving activation of cAMP-responsive element-binding protein. J Biol Chem 278, 51006-51014.
Kume, N., and Kita, T. (2001). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in atherogenesis. Trends Cardiovasc Med 11, 22-25.
Kumon, Y., Suehiro, T., Ikeda, Y., and Hashimoto, K. (2003). Human paraoxonase-1 gene expression by HepG2 cells is downregulated by interleukin-1beta and tumor necrosis factor-alpha, but is upregulated by interleukin-6. Life Sci 73, 2807-2815.
Lee, R. T., and Libby, P. (1997). The unstable atheroma. Arterioscler Thromb Vasc Biol 17, 1859-1867.
Lee, T. S., and Chau, L. Y. (2002). Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8, 240-246.
Leitinger, N., Tyner, T. R., Oslund, L., Rizza, C., Subbanagounder, G., Lee, H., Shih, P. T., Mackman, N.,Tigyi, G., Territo, M. C, et al. (1999). Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc Natl Acad Sci U S A 96, 12010-12015.
Leus, F. R., Zwart, M., Kastelein, J. J., and Voorbij, H. A. (2001). PON2 gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients. Atherosclerosis 154, 641-649.
Leviev, I., and James, R. W. (2000). Promoter polymorphisms of human paraoxonase PON1 gene and serum paraoxonase activities and concentrations. Arterioscler Thromb Vasc Biol 20, 516-521.
Libby, P. (2002). Inflammation in atherosclerosis. Nature 420, 868-874.
Lusis, A. J. (2000). Atherosclerosis. Nature 407, 233-241.
Mackness, B., Durrington, P., McEIduff, P., Yarnell, J., Azam, N., Watt, M., and Mackness, M. (2003). Low paraoxonase activity predicts coronary events in the Caerphilly Prospective Study. Circulation 107,2775-2779.
Mackness, M. I. (1989). 'A'-esterases. Enzymes looking for a role? Biochem Pharmacol 38, 385-390.
Mackness, M. I., Mackness, B., and Durrington, P. N. (2002). Paraoxonase and coronary heart disease.Atheroscler Suppl 3, 49-55.
Mackness, M. I., Mackness, B., Durrington, P. N., Fogelman, A. M., Berliner, J., Lusis, A. J., Navab, M.,
Shih, D., and Fonarow, G. C. (1998). Paraoxonase and coronary heart disease. Curr Opin Lipidol 9, 319-324.
Majesky, M. W. (2002). Mouse model for atherosclerotic plaque rupture. Circulation 105, 2010-2011.
Malin, R., Jarvinen, O., Sisto, T., Koivula, T., and Lehtimaki, T. (2001). Paraoxonase producing PON1 gene M/L55 polymorphism is related to autopsy-verified artery-wall atherosclerosis. Atherosclerosis 157,301-307.
Martinet, W., and Kockx, M. M. (2001). Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr Opin Lipidol 12, 535-541.
Mertens, A., and Holvoet, P. (2001). Oxidized LDL and HDL: antagonists in atherothrombosis. Faseb J 15,2073-2084.
Muller, K., Carpenter, K. L., and Mitchinson, M. J. (1998). Cell-mediated oxidation of LDL: comparison of different cell types of the atherosclerotic lesion. Free Radic Res 29, 207-220.
Navab, M., Berliner, J. A., Watson, A. D., Hama, S. Y., Territo, M. C., Lusis, A. J., Shih, D. M., Van Lenten,B. J., Frank, J. S., Demer, L. L., et al. (1996). The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture. Arterioscler Thromb Vasc Biol 16,831-842.
Navab, M., Hama-Levy, S., Van Lenten, B. J., Fonarow, G. C., Cardinez, C. J., Castellani, L. W., Brennan,M. L., Lusis, A. J., Fogelman, A. M., and La Du, B. N. (1997). Mildly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio. J Clin Invest 99, 2005-2019.
Ng, C. J., Bourquard, N., Grijalva, V., Hama, S., Shih, D. M., Navab, M., Fogelman, A. M., Lusis, A. J.,Young, S., and Reddy, S. T. (2006). Paraoxonase-2 deficiency aggravates atherosclerosis in mice despite lower apolipoprotein-B-containing lipoproteins: anti-atherogenic role for paraoxonase-2. J Biol Chem 281,29491-29500.
Ng, C. J., Bourquard, N., Hama, S. Y., Shih, D., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S.T. (2007). Adenovirus-mediated expression of human paraoxonase 3 protects against the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 27, 1368-1374.
Ng, C. J., Shih, D. M., Hama, S. Y., Villa, N., Navab, M., and Reddy, S. T. (2005). The paraoxonase gene family and atherosclerosis. Free Radic Biol Med 38, 153-163.
Ng, C. J., Wadleigh, D. J., Gangopadhyay, A., Hama, S., Grijalva, V. R., Navab, M., Fogelman, A. M., and Reddy, S. T. (2001). Paraoxonase-2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell-mediated oxidative modification of low density lipoprotein. J Biol Chem 276,44444.44449.
Nicholson, A. C., and Hajjar, D. P. (2004). CD36, oxidized LDL and PPAR gamma: pathological interactions in macrophages and atherosclerosis. Vascul Pharmacol 41, 139-146.
Nishio, E., and Watanabe, Y. (1997). Cigarette smoke extract inhibits plasma paraoxonase activity by modification of the enzyme's free thiols. Biochem Biophys Res Commun 236, 289-293.
Noris, M., Morigi, M., Donadelli, R., Aiello, S., Foppolo, M., Todeschini, M., Orisio, S., Remuzzi, G., and Remuzzi, A. (1995). Nitric oxide synthesis by cultured endothelial cells is modulated by flow conditions.Circ Res 76, 536-543.
Osaki, F., Ikeda, Y., Suehiro, T., Ota, K., Tsuzura, S., Arii, K., Kumon, Y., and Hashimoto, K. (2004). Roles of Sp1 and protein kinase C in regulation of human serum paraoxonase 1 (PON1) gene transcription in HepG2 cells. Atherosclerosis 176, 279-287.
Palombo, D., Maione, M., Cifiello, B. I., Udini, M., Maggio, D., and Lupo, M. (1999). Matrix metalloproteinases. Their role in degenerative chronic diseases of abdominal aorta. J Cardiovasc Surg(Torino) 40, 257-260.
Panini, S. R., and Sinensky, M. S. (2001). Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12,529-533.
Prager, G. W., and Binder, B. R. (2004). Genetic determinants: is there an "atherosclerosis gene"? Acta Med Austriaca 31, 1-7.
Primo-Parmo, S. L., Sorenson, R. C, Teiber, J., and La Du, B. N. (1996). The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family. Genomics 33, 498-507.
Rader, D. J., and Pure, E. (2005). Lipoproteins, macrophage function, and atherosclerosis: beyond the foam cell? Cell Metab 1, 223-230.
Rainwater, D. L., Mahaney, M. C., Wang, X. L., Rogers, J., Cox, L. A., and Vandeberg, J. L. (2005).Determinants of variation in serum paraoxonase enzyme activity in baboons. J Lipid Res 46, 1450-1456.
Reddy, S. T., Wadleigh. D. J., Grijalva, V., Ng, C., Hama, S., Gangopadhyay, A., Shih, D. M., Lusis, A. J.,Navab, M., and Fogelman, A. M. (2001). Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arterioscler Thromb Vasc Biol 21, 542-547.
Richter, R. J., and Furlong, C. E. (1999). Determination of paraoxonase (PONI) status requires more than genotyping. Pharmacogenetics 9, 745-753.
Rimm, E. B., and Stampfer, M. J. (2000). Antioxidants for vascular disease. Med Clin North Am 84,239-249.
Rosenblat, M., Draganov, D., Watson, C. E., Bisgaier, C. L., La Du, B. N., and Aviram, M. (2003). Mouse macrophage paraoxonase 2 activity is increased whereas cellular paraoxonase 3 activity is decreased under oxidative stress. Arterioscler Thromb Vasc Biol 23, 468-474.
Rosenblat, M., Hayek, T., Hussein, K., and Aviram, M. (2004). Decreased macrophage paraoxonase 2 expression in patients with hypercholesterolemia is the result of their increased cellular cholesterol content:effect of atorvastatin therapy. Arterioscler Thromb Vasc Biol 24, 175-180.
Rosenblat, M., Vaya, J., Shih, D., and Aviram, M. (2005). Paraoxonase 1 (PON 1) enhances HDL-mediated macrophage cholesterol efflux via the ABCA1 transporter in association with increased HDL binding to the cells: a possible role for lysophosphatidylcholine. Atherosclerosis 179, 69-77.
Ross, R. (1999). Atherosclerosis--an inflammatory disease. N Engl J Med 340, 115-126.
Rothwell, P. M., Villagra, R., Gibson, R., Donders, R. C., and Warlow, C. P. (2000). Evidence of a chronic systemic cause of instability of atherosclerotic plaques. Lancet 355, 19-24.
Schug, J., and Overton, G. C. (1997). Modeling transcription factor binding sites with Gibbs Sampling and Minimum Description Length encoding. Proc Int Conf Intell Syst Mol Biol 5, 268-271.
Schwartz, C. J., Valente, A. J., Sprague, E. A., Kelley, J. L., and Nerem, R. M. (1991). The pathogenesis of atherosclerosis: an overview. Clin Cardiol 14,11-16.
Schwartz, S. M., Galis, Z. S., Rosenfeld, M. E., and Falk, E. (2007). Plaque rupture in humans and mice.Arterioscler Thromb Vasc Biol 27, 705-713.
Schwenke, D. C., and Carew, T. E. (1989). Initiation of atherosclerotic lesions in cholesterol-fed rabbits. I.Focal increases in arterial LDL concentration precede development of fatty streak lesions. Arteriosclerosis 9,895-907.
Shih, D. M., Gu, L., Xia, Y. R., Navab, M., Li, W. F., Hama, S., Castellani, L. W., Furlong, C. E., Costa, L.G., Fogelman, A. M., and Lusis, A. J. (1998). Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature 394, 284-287.
Shih, D. M., Xia, Y. R., Wang, X. P., Miller, E., Castellani, L. W., Subbanagounder, G., Cheroutre, H., Faull,K. F., Berliner, J. A., Witztum, J. L., and Lusis, A. J. (2000). Combined serum paraoxonase knockout/apolipoprotein E knockout mice exhibit increased lipoprotein oxidation and atherosclerosis. J Biol Chem 275, 17527-17535.
Shih, D. M., Xia, Y. R., Wang, X. P., Wang, S. S., Bourquard, N., Fogelman, A. M., Lusis, A. J., and Reddy,S. T. (2007). Decreased obesity and atherosclerosis in human paraoxonase 3 transgenic mice. Circ Res 100,1200-1207.
Shireman, P. K., and Pearce, W. H. (1996). Endothelial cell function: biologic and physiologic functions in health and disease. AJR Am J Roentgenol 166, 7-13.
Sorenson, R. C, Bisgaier, C. L., Aviram, M., Hsu, C., Billecke, S., and La Du, B. N. (1999). Human serum Paraoxonase/Arylesterase's retained hydrophobic N-terminal leader sequence associates with HDLs by binding phospholipids : apolipoprotein A-I stabilizes activity. Arterioscler Thromb Vasc Biol 19, 2214-2225.
Steinberg, D. (1997). Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272, 20963-20966.
Steinberg, D., Parthasarathy, S., Carew, T. E., Khoo, J. C., and Witztum, J. L. (1989). Beyond cholesterol.Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320, 915-924.
Stemme, S., Faber, B., Holm, J., Wiklund, O., Witztum, J. L., and Hansson, G. K. (1995). T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. Proc Natl Acad Sci U S A 92,3893-3897.
Tabas, I. (2000). Cholesterol and phospholipid metabolism in macrophages. Biochim Biophys Acta 1529,164-174.
Teiber, J. F., Draganov, D. I., and La Du, B. N. (2003). Lactonase and lactonizing activities of human serum paraoxonase (PON1) and rabbit serum PON3. Biochem Pharmacol 66, 887-896.
Tomas, M., Senti, M., Elosua, R., Vila, J., Sala, J., Masia, R., and Marrugat, J. (2001). Interaction between the Gln-Arg 192 variants of the paraoxonase gene and oleic acid intake as a determinant of high-density lipoprotein cholesterol and paraoxonase activity. Eur J Pharmacol 432, 121-128.
Tsimihodimos, V., Karabina, S. A., Tambaki, A. P., Bairaktari, E., Goudevenos, J. A., Chapman, M. J.,Elisaf, M., and Tselepis, A. D. (2002). Atorvastatin preferentially reduces LDL-associated platelet-activating factor acetylhydrolase activity in dyslipidemias of type 1IA and type IIB. Arterioscler Thromb Vasc Biol 22,306-311.
Tward, A., Xia, Y. R., Wang, X. P., Shi, Y. S., Park, C., Castellani, L. W., Lusis, A. J., and Shih, D. M.(2002). Decreased atherosclerotic lesion formation in human serum paraoxonase transgenic mice. Circulation 106, 484-490.
van Berkel, T. J., Out, R., Hoekstra, M., Kuiper, J., Biessen, E., and van Eck, M. (2005). Scavenger receptors:friend or foe in atherosclerosis? Curr Opin Lipidol 16, 525-535.
van der Gaag, M. S., van Tol, A., Scheek, L. ML, James, R. W., Urgert, R., Schaafsma, G., and Hendriks, H.F. (1999). Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men. Atherosclerosis 147,405-410.
Van Lenten, B. J., Wagner, A. C., Navab, M., and Fogelman, A. M. (2001). Oxidized phospholipids induce changes in hepatic paraoxonase and ApoJ but not monocyte chemoattractant protein-1 via interleukin-6. J Biol Chem 276, 1923-1929.
Verhamme, P., Quarck, R., Hao, H., Knaapen, M., Dymarkowski, S., Bernar, H., Van Cleemput, J., Janssens,S., Vermylen, J., Gabbiani, G., et al. (2002). Dietary cholesterol withdrawal reduces vascular inflammation and induces coronary plaque stabilization in miniature pigs. Cardiovasc Res 56, 135-144.
Wallace, A. J., Sutherland, W. H., Mann, J. I., and Williams, S. M. (2001). The effect of meals rich in thermally stressed olive and safflower oils on postprandial serum paraoxonase activity in patients with diabetes. Eur J Clin Nutr 55, 951 -958.
Watanabe, T., Pakala, R., Koba, S., Katagiri, T., and Benedict, C. R. (2001). Lysophosphatidylcholine and reactive oxygen species mediate the synergistic effect of mildly oxidized LDL with serotonin on vascular smooth muscle cell proliferation. Circulation 103, 1440-1445.
Watson, A. D., Berliner, J. A., Hama, S. Y., La Du, B. N., Faull, K. F., Fogelman, A. M., and Navab, M.(1995). Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest 96, 2882-2891.
Watzinger, N., Schmidt, H., Schumacher, M., Schmidt, R., Eber, B., Fruhwald, F. M., Zweiker, R., Kostner,G. M., and Klein, W. (2002). Human paraoxonase 1 gene polymorphisms and the risk of coronary heart disease: a community-based study. Cardiology 98, 116-122.
Witztum, J. L., and Steinberg, D. (1991). Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88, 1785-1792.
Yamada, Y., Doi, T., Hamakubo, T., and Kodama, T. (1998). Scavenger receptor family proteins: roles for atherosclerosis, host defence and disorders of the central nervous system. Cell Mol Life Sci 54, 628-640.
Yang, C. M., Chien, C. S., Hsiao, L. D., Pan, S. L., Wang, C. C., Chiu, C. T., and Lin, C. C. (2001).Mitogenic effect of oxidized low-density lipoprotein on vascular smooth muscle cells mediated by activation of Ras/Raf/MEK/MAPK pathway. Br J Pharmacol 132, 1531-1541.
Yusuf, S., Dagenais, G., Pogue, J., Bosch, J., and Sleight, P. (2000). Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.N Engl J Med 342, 154-160.
Zettler, M. E., Prociuk, M. A., Austria, J. A., Zhong, G., and Pierce, G. N. (2004). Oxidized low-density lipoprotein retards the growth of proliferating cells by inhibiting nuclear translocation of cell cycle proteins.Arterioscler Thromb Vasc Biol 24, 727-732.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |