坎地沙坦干预大鼠动脉粥样硬化作用及机制的实验研究
|
摘要
目的:
本研究通过建立大鼠动脉粥样硬化病理模型,观察坎地沙坦对动脉粥样硬化的干预作用,并探讨其可能的作用机制。
方法:
雄性、10周龄SD大鼠,随机分为5组:正常组(A组)、模型组(B组)、坎地沙坦低(1 mg.kg-1.d-1,C组)、中(5 mg.kg-1.d-1,D组)、高(10 mg.kg-1.d-1,E组)剂量组。B、C、D、E组均饲喂高脂饲料,配合一次性腹腔注射维生素D3建立大鼠AS模型。A组饲喂普通饲料,腹腔注射等体积生理盐水。坎地沙坦干预组自造模第一天开始灌胃,A、B组给予等量生理盐水灌胃饲养12周。光镜下HE染色观察腹主动脉病理改变,透射电镜下观察超微结构的改变。腹腔静脉取血,生化方法检测血脂、MDA、SOD、酶联免疫吸附双抗体夹心方法检测oxLDL。免疫组织化学的方法检测腹主动脉MMP-2、VEGF的表达。
结果:
1、B组血清TG水平高于A组,HDL水平低于A组(P<0.01)。C、D、E组血清TG水平均比B组下降(P<0.05,P<0.01),但三组间无差别(P>0.05),E组HDL比B组显著升高(P<0.01)。对于TG / HDL来说B组显著高于A组(P<0.05),E组较B组显著下降(P<0.05);C、D组较B组有所下降但差异无统计学意义(P>0.05)。
2、模型组与正常组相比主动脉出现动脉粥样硬化的形态学改变;与模型组相比坎地沙坦低、中、高剂量组动脉粥样硬化的形态学改变有所减轻。
3、B组大鼠血清MDA水平高于A组,两者差异有统计学意义(P<0.01);C、D组血清中MDA水平比B组降低,但差异没有统计学意义(P>0.05);E组能明显降低大鼠血清中MDA水平,与B组相比,差异有统计学意义(P<0.01)。B组大鼠血清SOD水平低于A照组,两者差异有统计学意义(P<0.01);E组能明显升高大鼠血清中SOD水平,与B组相比,差异有统计学意义(P<0.05)。
4、血清oxLDL水平(ng/dl)B组大鼠高于A组,差异有统计学意义(P<0.01)。C组、D组、E组的血清oxLDL水平与B组相比明显降低,差异有统计学意义(P<0.01)。但C、D、E组之间无差别(P>0.05)。
5、血管MMP-2的表达:D、E组较B组均减少(P<0.05);但B、C组间无差别(P>0.05),D、E组间无差别(P>0.05)。血管VEGF的表达:C、D、E组较B组均减少(P<0.05);D、E组较C组减少(P<0.05),但D、E组间无差别(P>0.05)。
结论:
1、坎地沙坦可以调节AS大鼠的血脂紊乱并减轻AS大鼠主动脉病理改变。
2、坎地沙坦可以降低AS大鼠血清MDA水平、升高SOD水平;而且可以降低大鼠血清中的oxLDL水平。
3、坎地沙坦通过减少AS大鼠血管MMP-2、VEGF的表达改善AS发生过程中血管的重塑。
Objects:
To investigate the anti-atherosclerosis effects and mechanism of Candesartan on experimental atherosclerosis rats.
Methods:
Male SD rats of ten-months were randomly divided into 5 groups:A(normal rats),B(atherosclerosis rats),C(atherosclerosis rats fed with candesartan 1 mg.kg-1.d-1), D(atherosclerosis rats fed with candesartan 5 mg.kg-1.d-1) and E(atherosclerosis rats fed with candesartan 10mg.kg-1.d-1). The rats of group B,C,D,E were fed with high lipid feedstuff and received intraperitoneal injection of vitamin D3 at one time. The rats of group A were fed with nomal feedstuff and injected the saline with the same dose. Candesartan was given to the rats of group C,D,E by gavage from the beginning to the end of the experiment. At the same time rats of groupA and B were given the saline of same dose by gavage. After 12 weeks,the same arteries of rats of each group were examined by HE staining and electron microscope.The lipid indexes, MDA and SOD were determined by biochemistry method.OxLDL in serum of each group rats was measured by ELISA. The expressions of MMP-2 and VEGF in aorta were determined by immunohistochemistry.
Result:
1 The TG in groupC,D and E was lower than those in group B without a dose-dependent manner(P<0.05,P<0.01).Compared with groupB,HDL increased significantly( P< 0. 05) in the group E. The TG / HDL in the group E decreased significantly( P< 0. 05).
2 Compared with groupA, morphological changes of Atherosclerosis in the arteries of group B were observed.Compared with group B, morphological changes of atherosclerosis of groupC,D and E lightened significantly.
3 Compared with group A,the MDA and SOD were significantly different in the group B ( P<0.01).The MDA in group E was lower than those in the group B ( P<0.01).Compared with group B, SOD increased significantly( P< 0. 05) in the group E.
4 The oxLDL in groups of C,D and E were lower than those in group B without a dose- dependent manner(P<0.01).
5 Compared with group B, the expressions of MMP-2 in aorta decreased in groups of D and E(P<0.05). Compared with group B, the expressions of VEGF in aorta decreased in groups of C,D and E(P<0.05).
Conclusion:
1 Candesartan can regulate the disorder of blood lipids and influence the morphology of artery in atherosclerosis rats.
2 Candesartan can increase SOD and decrease MDA and oxLDL remarkably of blood serum in atherosclerosis rats.
3 Candesartan appeares to markedly reduce the expressions of MMP-2 and VEGF of aorta in atherosclerosis rats.
本研究通过建立大鼠动脉粥样硬化病理模型,观察坎地沙坦对动脉粥样硬化的干预作用,并探讨其可能的作用机制。
方法:
雄性、10周龄SD大鼠,随机分为5组:正常组(A组)、模型组(B组)、坎地沙坦低(1 mg.kg-1.d-1,C组)、中(5 mg.kg-1.d-1,D组)、高(10 mg.kg-1.d-1,E组)剂量组。B、C、D、E组均饲喂高脂饲料,配合一次性腹腔注射维生素D3建立大鼠AS模型。A组饲喂普通饲料,腹腔注射等体积生理盐水。坎地沙坦干预组自造模第一天开始灌胃,A、B组给予等量生理盐水灌胃饲养12周。光镜下HE染色观察腹主动脉病理改变,透射电镜下观察超微结构的改变。腹腔静脉取血,生化方法检测血脂、MDA、SOD、酶联免疫吸附双抗体夹心方法检测oxLDL。免疫组织化学的方法检测腹主动脉MMP-2、VEGF的表达。
结果:
1、B组血清TG水平高于A组,HDL水平低于A组(P<0.01)。C、D、E组血清TG水平均比B组下降(P<0.05,P<0.01),但三组间无差别(P>0.05),E组HDL比B组显著升高(P<0.01)。对于TG / HDL来说B组显著高于A组(P<0.05),E组较B组显著下降(P<0.05);C、D组较B组有所下降但差异无统计学意义(P>0.05)。
2、模型组与正常组相比主动脉出现动脉粥样硬化的形态学改变;与模型组相比坎地沙坦低、中、高剂量组动脉粥样硬化的形态学改变有所减轻。
3、B组大鼠血清MDA水平高于A组,两者差异有统计学意义(P<0.01);C、D组血清中MDA水平比B组降低,但差异没有统计学意义(P>0.05);E组能明显降低大鼠血清中MDA水平,与B组相比,差异有统计学意义(P<0.01)。B组大鼠血清SOD水平低于A照组,两者差异有统计学意义(P<0.01);E组能明显升高大鼠血清中SOD水平,与B组相比,差异有统计学意义(P<0.05)。
4、血清oxLDL水平(ng/dl)B组大鼠高于A组,差异有统计学意义(P<0.01)。C组、D组、E组的血清oxLDL水平与B组相比明显降低,差异有统计学意义(P<0.01)。但C、D、E组之间无差别(P>0.05)。
5、血管MMP-2的表达:D、E组较B组均减少(P<0.05);但B、C组间无差别(P>0.05),D、E组间无差别(P>0.05)。血管VEGF的表达:C、D、E组较B组均减少(P<0.05);D、E组较C组减少(P<0.05),但D、E组间无差别(P>0.05)。
结论:
1、坎地沙坦可以调节AS大鼠的血脂紊乱并减轻AS大鼠主动脉病理改变。
2、坎地沙坦可以降低AS大鼠血清MDA水平、升高SOD水平;而且可以降低大鼠血清中的oxLDL水平。
3、坎地沙坦通过减少AS大鼠血管MMP-2、VEGF的表达改善AS发生过程中血管的重塑。
Objects:
To investigate the anti-atherosclerosis effects and mechanism of Candesartan on experimental atherosclerosis rats.
Methods:
Male SD rats of ten-months were randomly divided into 5 groups:A(normal rats),B(atherosclerosis rats),C(atherosclerosis rats fed with candesartan 1 mg.kg-1.d-1), D(atherosclerosis rats fed with candesartan 5 mg.kg-1.d-1) and E(atherosclerosis rats fed with candesartan 10mg.kg-1.d-1). The rats of group B,C,D,E were fed with high lipid feedstuff and received intraperitoneal injection of vitamin D3 at one time. The rats of group A were fed with nomal feedstuff and injected the saline with the same dose. Candesartan was given to the rats of group C,D,E by gavage from the beginning to the end of the experiment. At the same time rats of groupA and B were given the saline of same dose by gavage. After 12 weeks,the same arteries of rats of each group were examined by HE staining and electron microscope.The lipid indexes, MDA and SOD were determined by biochemistry method.OxLDL in serum of each group rats was measured by ELISA. The expressions of MMP-2 and VEGF in aorta were determined by immunohistochemistry.
Result:
1 The TG in groupC,D and E was lower than those in group B without a dose-dependent manner(P<0.05,P<0.01).Compared with groupB,HDL increased significantly( P< 0. 05) in the group E. The TG / HDL in the group E decreased significantly( P< 0. 05).
2 Compared with groupA, morphological changes of Atherosclerosis in the arteries of group B were observed.Compared with group B, morphological changes of atherosclerosis of groupC,D and E lightened significantly.
3 Compared with group A,the MDA and SOD were significantly different in the group B ( P<0.01).The MDA in group E was lower than those in the group B ( P<0.01).Compared with group B, SOD increased significantly( P< 0. 05) in the group E.
4 The oxLDL in groups of C,D and E were lower than those in group B without a dose- dependent manner(P<0.01).
5 Compared with group B, the expressions of MMP-2 in aorta decreased in groups of D and E(P<0.05). Compared with group B, the expressions of VEGF in aorta decreased in groups of C,D and E(P<0.05).
Conclusion:
1 Candesartan can regulate the disorder of blood lipids and influence the morphology of artery in atherosclerosis rats.
2 Candesartan can increase SOD and decrease MDA and oxLDL remarkably of blood serum in atherosclerosis rats.
3 Candesartan appeares to markedly reduce the expressions of MMP-2 and VEGF of aorta in atherosclerosis rats.
引文
[1]金晓明,李玉林,唐建武,等.病理学[M].第六版.北京:人民卫生出版社,2008.130.
[2] Antonio C, Peter T. PPARs in atherosclerosis: the clot thickens [J].J Clin Invest,2004,114(11): 1538-1540.
[3] Jaber J, Murin J, Kinova S, et al.The role of infection and inflammation in the pathogenesis of athero-sclerosis [J]. Vnitr Lek, 2002,48(7) : 657-666.
[4]李颖莉.低密度脂蛋白受体相关蛋白与动脉粥样硬化的关系[J].中国分子心脏病学杂志,2003, 3(3):167-173.
[5] Yong IS , McEneny J . Lipoprotein oxidation and atherosclerosis [J] .Biochem Soc Trans,2001, 29(2): 358 -362.
[6] Mehta J K, Chen J , Hermonat P L,et al. Lectinlike oxidized low- density lipoprotein receptor-1 (LOX-1) :A critical player in the development of atherosclerosis and related disorders[J]. Cardiovasc Res, 2006, 69(1):36-45 .
[7]李素敏.弱氧化型低密度脂蛋白的致动脉粥样硬化作用[J].中国动脉硬化杂志, 2002, 10(3): 271-274.
[8] Ma JL,Yang PY,Rui YC,et al. Hemin modulates cytokine expressions in macrophagederived foam cells via heme oxygenase-1 induction[J]. J Pharmacol Sci, 2007, 103(3):261-266.
[9] Jiang G, Li T, Qiu Y, et al. RNA interference for HIF-1alpha inhibits foam cells formation in vitro[J]. Eur J Pharmacol, 2007, 562(3):183-190.
[10] Ji SR, Wu Y, Potempa LA, et al. Interactions of C-reactive protein with low-density lipo-proteins: implications for an active role of modified C-reactiveprotein in atherosclerosis[J]. Int J Biochem Cell Biol,2006, 38(4):648-661.
[11] Navab M.The oxidation hypothesis of atherogenesis:the role of oxidized phospholipids [J]. J Lipid Res,2004,45(6):993 -1007.
[12] Quan Z, Yang H, Yang Y, et al. Construction and functional analysis of a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds uniquely phosphatidylserine and oxidized lipoprotein[J].Acta Biochim Biophys Sin (Shanghai),2007, 39(3):208-216.
[13] Rahaman SO, Lennon DJ, Febbraio M, et al. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation[J]. Cell Metab, 2006,4(3):211-421.
[14] Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome[J]. Vasc Health Risk Manag, 2005, 1(3):183-198.
[15] Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis[J]. Circulation, 2004, 109(23):Ⅲ27-32.
[16] GengY J,Libby P. Progression of atheroma: a struggle between death and procreation [J]. A rterioscler Thromb Vasc Biol, 2002, 22 (9): 1370-1380.
[17] Porn-AresM I, Saido T C, Andersson T, et al. Oxidized LDL induces calpain-dependent cell death and ubiquitina-tion of caspase 3 in HMEC-1endothelial cells [J]. Biohem J, 2003,374(2):403-411.
[18] Jiang Y, Zhang J, Xiong J, et al. Ligands of Peroxisome Proliferator-activated Receptor inhibit Homocysteine-induced DNA Methylation of Inducible Nitric Oxide Synthase Gene[J]. Acta Biochim Biophys Sin(Shanghai), 2007, 39(5):366-376.
[19] Naseem KM. The role of nitric oxide in cardiovasculardiseases[J]. Mol Aspects Med, 2005, 26(1):33-65.
[20]何翠瑶,李晓辉,李淑惠,等.三七皂苷对氧化低密度脂蛋白损伤血管内皮细胞保护作用的研究[J].中国药房, 2008,19(6):401-403.
[21] Millette E, Rauch BH, Defawe O, et al. Platelet-derived growth factor-BB-induced human smooth muscle cell proliferation depends on basic FGF release and FGFR-1 activation[J]. Circ Res, 2005, 96(2): 172-179.
[22] Vindis C, Escargueil-Blanc I, Uchida K, et al.Lipid oxidation products and oxidized low-density lipoproteins impair platelet-derived growth factor receptor activity in smooth muscle cells: implication in atherosclerosis[J]. Redox Rep, 2007, 12(1):96-100.
[23] Akishima Y, Akasaka Y, Ishikawa Y, et al. Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development[J]. Mod Pathol,2005,18(3):365-373.
[24] Lupo G, Nicotra A, Giurdanella G, et al. Activation of phospholipase A(2) and MAP kinases by oxidized low-density lipoproteins in immortalized GP8. 39 endothelial cells[J].B iochim B iophys Ac-ta, 2005,1735(2):135-50.
[25] Shibata Y, Kume N, Arai H, et al. Mulberry leaf aqueous fractions inhibit TNF-alphainduced nuclear factor kappaB (NF-kappaB) activation and lectinlike oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells[J]. Atherosclerosis, 2007,193(1):20-27.
[26] Ruan XZ, Moorhead JF, Tao JL, et al. Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines[J]. Arterioscler Thromb Vasc Biol, 2006,26(5):1150-1155.
[27] Kaneyuki U, Ueda S, Yamagishi S, et al. Pitavastatin inhibits lysophosphatidic acid-induced pro-liferation and monocyte chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing Rac-1-mediated reactive oxygen species generation[J].Vascul Pharmacol, 2007, 46(4): 286-292.
[28]张清华,赖晓辉,蒋知新.血管内皮细胞功能与氧化低密度脂蛋白的影响[J].中国组织工程研究与临床康复, 2007,11(6):1174-1176.
[29] Dotevall A , Hult he J ,Rosengren A ,et al . Autoantibodies against oxidized low density lipoprotein and C - reactive protein are associated wit h diabetes and myocardial infarction in women[J].Clin Sci (lond) ,2001,101(5):523–531.
[30] Mironova MA,Klein RL,Virella GT,et al.Anti–modified LDL antibodies LDL-containing immunance complexes and susceptibility of LDL to in vitro oxidation in patients with Type-diabetes[J]. Diabetes, 2000,49(6) :1033–1041.
[31] Raitakari OT ,Pit kanen OP ,Lehtimaki T,et al . Autoantibody against oxidized LDL and LDL article size : relationships to coronary reactivity in young men [J] . J Am Coll Cardiol,1997,30(11):97–102.
[32] Naghavi M ,Libbey P ,Falk E ,et al . Form vulnerable plaque to vulnerable patient a call for new definitions and risk assessment st- rategies : PartⅠ[J]. Circulation, 2003,108(14) : 1664 -1672.
[1] Liuzzo G. Atherosclerosis-an inflammatory disease[J]. N Engl J Med. 2001,26(4):221–230.
[2] Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis[J]. Arterioscler Thromb Vasc Biol. 2007, 27(11):2292–301.
[3] Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis[J]. J Clin Invest. 2001,107(13):1255–62.
[4] Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques[J]. J Clin Invest. 2007,117(1)185–94.
[5] Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata[J]. J Clin Invest. 2007,117(1):195–205.
[6] Saederup N, Chan L, Lira SA, Charo IF. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2?/? mice: evidence for independent chemokine functions in atherogenesis[J]. Circulation. 2008,117(13):1642–48.
[7] Mantovani A, Sica A, Locati M. Macrophage polarization comes of age[J]. Immunity. 2005,23(4):344–46.
[8] Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice[J]. J Clin Invest. 2000,105(8):1049–56.
[9] Moore KJ, Kunjathoor VV, Koehn SL, Manning JJ, Tseng AA, et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice[J]. J Clin Invest. 2005,115(8):2192–201.
[10] Stoneman V, Braganza D, Figg N, Mercer J, Lang R, et al. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques[J]. Circ Res. 2007,100(6):884–93.
[11] Byrne GI, Kalayoglu MV. Chlamydia pneumoniae and atherosclerosis: links to the disease proces[sJ]. Am Heart J. 1999,138(5):S488–S490.
[12] Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency[J]. Arterioscler Thromb Vasc Biol. 2005,25(11):2255–64.
[13] Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, et al. Phospholipase Cβ3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice[J]. J Clin Invest. 2008,118(1):195–204.
[14] Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, et al. Lack of macrophage fatty- acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis[J]. Nat Med. 2001,7(6):699–705.
[15] Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, et al. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice[J]. J Clin Invest. 2007,117(12):3900–8.
[16] Zhao B, Song J, Chow WN, St Clair RW, Rudel LL, Ghosh S. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr?/? mice[J]. J Clin Invest. 2007,117(10):2983–92.
[17]林蓉,甘伟杰.药物治疗动脉粥样硬化新途径-抗炎作用[ J ].中国药理学通报, 2004, 20 (5): 499-502.
[18] Erbel C, Sato K, Meyer FB, Kopecky SL, Frye RL, et al. Functional profile of activated dendritic cells in unstable atherosclerotic plaque[J]. Basic Res Cardiol. 2007,102(2):123–32.
[19] Perrin-Cocon L, Coutant F, Agaugue S, Deforges S, Andre P, Lotteau V. Oxidized low-density lipoprotein promotes mature dendritic cell transition from differentiating monocyte[J]. J Immunol. 2001,167(7):3785–91.
[20] Maffia P, Zinselmeyer BH, Ialenti A, Kennedy S, Baker AH, et al. Images in cardiovascular medicine. Multiphoton microscopy for 3-dimensional imaging of lymphocyte recruitment into apolipoprotein-E- deficient mouse carotid artery[J]. Circulation. 2007,115(11):326–28.
[21] Zhou X, Paulsson G, Stemme S, Hansson GK. Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice. [J] J Clin Invest. 1998,101(8):1717–25.
[22] Whitman SC, Ramsamy TA. Participatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studies[J]. Can J Physiol Pharmacol. 2006,84(1):67–75.
[23] Lindstedt KA, Mayranpaa MI, Kovanen PT. Mast cells in vulnerable atherosclerotic plaques-a view to a kill[J]. J Cell Mol Med. 2007,11(4):739–58.
[24] Lee M, Calabresi L, Chiesa G, Franceschini G, Kovanen PT. Mast cell chymase degrades apoE and apoA-II in apoA-I-knockout mouse plasma and reduces its ability to promote cellular cholesterol efflux[J]. Arterioscler Thromb Vasc Biol. 2002,22(9):1475–81.
[25] Sun J, Sukhova GK, Wolters PJ, Yang M, Kitamoto S, et al. Mast cells promote atherosclerosis by releasing proinflammatory cytokines[J]. Nat Med. 2007,13(6):719–24.
[26] Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice[J]. J Clin Invest. 2002,109(6):745–53.
[27] Zernecke A, Bot I, Djalali-Talab Y, Shagdarsuren E, Bidzhekov K, et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis[J]. Circ Res. 2008,102(2):209–17.
[28] von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease[J]. Circ Res. 2007,100(1):27–40.
[29] Burger PC, Wagner DD. Platelet P-selectin facilitates atherosclerotic lesion development[J]. Blood. 2003,101(7):2661–66.
[30] Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E[J]. Nat Med. 2003;9(1):61–67.
[31] Langer HF, Daub K, Braun G, Schonberger T, May AE, et al. Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro[J]. Arterioscler Thromb Vasc Biol. 2007,27(6):1463–70.
[32] Schulz C, Schafer A, Stolla M, Kerstan S, Lorenz M, et al. Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood: a critical role for P-selectin expressed on activated platelets[J]. Circulation. 2007,116(7):764–73.
[33] Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways[J]. Physiol Rev. 2006,86(2):515–81.
[34] Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and athero- sclerotic plaque rupture[J]. Physiol Rev. 2005,85(1):1–31.
[35] Moreno PR, Purushothaman KR, Sirol M, Levy AP, Fuster V. Neovascularization in human athero-sclerosis[J]. Circulation. 2006,113(11):2245–52.
[36] Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, et al. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites[J]. J Clin Invest. 2007,117(4):902–9.
[37] Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B [ J ] . J Clin Invest. 1999,103(6):773–78.
[38] Yu G, Rux AH, Ma P, Bdeir K, Sachais BS. Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-κB-dependent manner[J]. Blood. 2005,105(9):3545–51.
[39] Kuziel WA, Dawson TC, Quinones M, Garavito E, Chenaux G, et al. CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice[J]. Atherosclerosis. 2003,167(1):25–32.
[40] Braunersreuther V, Zernecke A, Arnaud C, Liehn EA, Steffens S, et al. Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol. 2007,27(2):373–79.
[41] Huo Y, Weber C, Forlow SB, Sperandio M, Thatte J, et al. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium[J]. J Clin Invest. 2001,108(9):1307–14.
[42] Cheng C, Tempel D, van HR, de Boer HC, Segers D, et al. Shear stress-induced changes in athero- sclerotic plaque composition are modulated by chemokines[J]. J Clin Invest.2007,117(3):616–26.
[43] Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment[J]. Nat Med. 2007, 13(5):587–96.
[44] Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, et al. Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice[J]. Circulation. 2004,109(25):3149-53.
[45] Kraaijeveld AO, de Jager SC, van Berkel TJ, Biessen EA, Jukema JW. Chemokines and atherosclerotic plaque progression: towards therapeutic targeting? [J ] . Curr Pharm Des. 2007,13(10):1039–52.
[46] Aslanian AM, Charo IF. Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis[J]. Circulation. 2006,114(6):583-90.
[47] Galkina E, Harry BL, Ludwig A, Liehn EA, Sanders JM, et al. CXCR6 promotes atherosclerosis by supporting T-cell homing, interferon-γproduction, and macrophage accumulation in the aortic wall[J]. Circulation. 2007,116(16):1801–11.
[1]温进坤,韩梅,杜玮南,等.一种快速建立大鼠动脉粥样硬化模型的实验方法[J].中国老年学杂志,2001,21(1) : 50-52.
[2]金晓明,李玉林,唐建武,等.病理学[M].第六版.北京:人民卫生出版社,2008.130.
[3]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报,1996, 27(2): 133-135.
[4]雷大洲,韩清华.TC/HDL-C比值在冠心病诊断中的应用[J].中西医结合心血管病杂志,2009,63(2):63-65.
[5]曲勇,王伟玲,廖琳.ARB降压改善胰岛素敏感性的研究[J].实用糖尿病杂志,2006,2(5):17-18.
[6]王兆宏,陈还珍,李晓英,等.坎地沙坦西酯治疗高血压合并糖代谢异常病人临床研究[J].中西医结合心脑血管病杂志,2008,6(1) :16-18.
[7] Davis BN,Hilyard AC,Nguyen PH,et al. Induction of microRNA- 221 by platelet-derived growth factor signaling is critical formodulation of vascular smooth muscle phenotype [J]. J Biol Chem,2009 284(6): 3728-3738.
[8]李薇,杜军保.动脉粥样硬化发病机制研究进展[J].实用儿科临床杂志, 2009,24(1):58-60.
[9]黄书攀,陈坤赞.坎地沙坦西酯治疗原发性高血压的疗效及对心血管重构的影响[J].全科医学临床与教育,2008,6(2):112.
[10] Suzuki J, Iwai M, Horiuchi M et al. Role of angiotensin II regulated apoptosis through distinct AT1 and AT2 receptors in neointimal formation[J]. Circulation, 2002, 106(7):847-853.
[11] Okumura M, Iwai M, Horiuchi M. Sex difference in vascular injury and the vasoprotective effect of valsartan are related to differential AT2 receptor expression[J].Hypertension, 2005,46(3) 577-583.
[1]朱宝亮,葛顺,刘霞.氧化应激与动脉粥样硬化研究进展[ J].济宁医学院学报,2009,32(5):373-375.
[2] ShinMH,MoonYJ,Seo JE, eta.l Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrialelectron transportsystem mediate heat shock-induced MMP-1 and MMP-9 expression [ J]. FreeRadicBiolMed,2008,44(4): 635-645.
[3]朱晔斌,吴双,孔麟麟,等.氧化型低密度脂蛋白的形成及其致动脉粥样硬化的机制[J].武警医学院学报,2009,18(11):62-64.
[4]李震霄,邹洪梅.氧化应激促进动脉粥样硬化机制研究进展[J].中国动脉硬化杂志,2009, 17(8):702-705.
[5] MadamanchiNR,RungeMS.Mitochondrial dysfunction in atherosclerosis [J].CircRes,2007,100(4): 460-473.
[6] Roucou X, Antonsson B, Martinou JC.Involvement of mitochondria inapoptosis[J].CardiolClin, 2001,19(1): 45-55.
[7] Cai H, Harrison D G. Endothelial dysfunction in cardiovascular disease: the role of oxidant stress[ J ]. Circ Res, 2000, 87(8): 840 - 844.
[8] Kolodgie F D, Gold H K, Burke A P, et al. Intraplaque Hemorrhage and Progression of Coronary Atheroma [ J ].N Engl J Med, 2003, 349(24): 2285-2287.
[9] Sowers J R. Hypertension, angiotensinⅡ, and oxidative stress[J]. N Engl J Med, 2002, 346(3): 1999 - 2001.
[10] McCormickML,Gavrila D,Weintraub NL. Role of oxidative stress in the pathogenesis of abdominal aortic aneuysms[ J ]. Arterioscler Thromb Vasc Biol, 2007,27 (3) : 461-469.
[11] Matsuura E, Kobayashi K, TabuchiM, et al. Oxidative modification of low density lipoprotein and immune regulation of atherosclerosis [ J ]. Prog Lipid Res,2006, 45 (6) : 466-486.
[12] OgawaS,Mori T, Nako K, et al. AngiotensinⅡtype 1 receptor blockers reduce urinary oxidative stressmarkers in hypertensive diabetic nephropathy[ J ]. Hypertension, 2006, 47 (4) : 699 - 705.
[13]林桦.血管紧张素Ⅱ1型受体拮抗剂坎地沙坦的研究进展[ J ].海峡药学,2009,21 (10):9-12.
[14] Mehta JK, Chen J, Hermonat P L,et al. Lectinlike oxidized low- density lipoprotein receptor-1 (LOX-1):A critical player in the development of atherosclerosis and related disorders[J]. Cardiovasc Res,2006,69(1):36-45.
[15] Ma JL,Yang PY,Rui YC,et al. Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction[J]. J Pharmacol Sci,2007,10(3):261-266.
[16]何翠瑶,李晓辉,李淑惠,等.三七皂苷对氧化低密度脂蛋白损伤血管内皮细胞保护作用的研究[J].中国药房, 2008,19(6):401-403.
[17] Berry C,Hamiton CA,Brosnan MJ,et al.Investigation into the source of Super-oxide in human blood vessels:angiotensinⅡincrease superoxide production in human internal mammary arteries[J]. Circulation, 2000,101(3):2206-2212.
[18] Limor R,Kaplan M,Sawamura T,et al.AngiotensinⅡincrease the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway[J].Am J Hypertens,2005,18(3):299-307.
[19] Galle J,Mameghani A,Bolz SS,et al.Oxidized LDL and its compound lysophosphatidylcholine potentiate AngⅡ-induced vasoconstiction by stimulation of RhoA[J].J Am Soc Nephrol,2003,14(6): 1471-1479.
[20] Urata H,Nishimura H,Ganten D.Chymase-dependent angiotensinⅡforming system in humans[J].Am J Hypertens,1996,9(3):277-284.
[1]张伟丽,惠汝太.VEGF及其受体在动脉粥样硬化中的作用[J].中国分子心脏病学杂志,2005,2(5):568-573.
[2] RamosMA, Kuzuya M, Esaki T, et al.Induction of macrophage VEGF in response to oxidized LDL and VEGFaccumulation in human atherosclerotic lesions.ArteriosclerThromb Vasc Biol, 1998,18(7):1 188-1196.
[3]赵瑾,迟路湘,陈德英.基质金属蛋白酶-2在兔颈动脉内膜损伤后动脉粥样硬化斑块中的表达[J].第三军医大学学报,2006,28(8):792-794.
[4]卢维晟,王一尘. MMP22表达与大鼠动脉粥样硬化和血管钙化的关系及辛伐他汀对其影响[J].心脏杂志,2006,18(4):376-378.
[5] Jahnson JL,Baker AH,Oka K,et al.Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2[J].Circulation,2006,113(20):2435-2444.
[6] Luchtefeld M,Grote K,Grothusen C,et al.Angiotensin II induces MMP-2 in p47phox-dependent manner[J]. Biochem Biophys Res Commun,2005,328(1):183-188.
[7] Guo RW,Yang LX,Wang H,et al.Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells[J].Regul Pept,2008, 147(13):37-44.
[8] Xie TX,Wei D,Liu M,et al.Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis[J].Oncogene,2004,23(20):3550-3560.
[9] Raymond L,Eck S,Mollmark J,et al.Interleukin-1 beta induction of matrix metalloproteinase-1 transcription in chondrocytes requires ERK-dependent activation of CCAAT enhancer-binding protein-beta[J].J Cell Physiol,2006, 207(3):683-688.
[10] Celletti FL,Waugh JM,Amabile PG,et al.Vascular endothelial growth factor enhances atherosclerotic plaque progression[J].Nat Med,2001,7(4):425-429.
[2] Antonio C, Peter T. PPARs in atherosclerosis: the clot thickens [J].J Clin Invest,2004,114(11): 1538-1540.
[3] Jaber J, Murin J, Kinova S, et al.The role of infection and inflammation in the pathogenesis of athero-sclerosis [J]. Vnitr Lek, 2002,48(7) : 657-666.
[4]李颖莉.低密度脂蛋白受体相关蛋白与动脉粥样硬化的关系[J].中国分子心脏病学杂志,2003, 3(3):167-173.
[5] Yong IS , McEneny J . Lipoprotein oxidation and atherosclerosis [J] .Biochem Soc Trans,2001, 29(2): 358 -362.
[6] Mehta J K, Chen J , Hermonat P L,et al. Lectinlike oxidized low- density lipoprotein receptor-1 (LOX-1) :A critical player in the development of atherosclerosis and related disorders[J]. Cardiovasc Res, 2006, 69(1):36-45 .
[7]李素敏.弱氧化型低密度脂蛋白的致动脉粥样硬化作用[J].中国动脉硬化杂志, 2002, 10(3): 271-274.
[8] Ma JL,Yang PY,Rui YC,et al. Hemin modulates cytokine expressions in macrophagederived foam cells via heme oxygenase-1 induction[J]. J Pharmacol Sci, 2007, 103(3):261-266.
[9] Jiang G, Li T, Qiu Y, et al. RNA interference for HIF-1alpha inhibits foam cells formation in vitro[J]. Eur J Pharmacol, 2007, 562(3):183-190.
[10] Ji SR, Wu Y, Potempa LA, et al. Interactions of C-reactive protein with low-density lipo-proteins: implications for an active role of modified C-reactiveprotein in atherosclerosis[J]. Int J Biochem Cell Biol,2006, 38(4):648-661.
[11] Navab M.The oxidation hypothesis of atherogenesis:the role of oxidized phospholipids [J]. J Lipid Res,2004,45(6):993 -1007.
[12] Quan Z, Yang H, Yang Y, et al. Construction and functional analysis of a lentiviral expression vector containing a scavenger receptor (SR-PSOX) that binds uniquely phosphatidylserine and oxidized lipoprotein[J].Acta Biochim Biophys Sin (Shanghai),2007, 39(3):208-216.
[13] Rahaman SO, Lennon DJ, Febbraio M, et al. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation[J]. Cell Metab, 2006,4(3):211-421.
[14] Hadi HA, Carr CS, Al Suwaidi J. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome[J]. Vasc Health Risk Manag, 2005, 1(3):183-198.
[15] Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis[J]. Circulation, 2004, 109(23):Ⅲ27-32.
[16] GengY J,Libby P. Progression of atheroma: a struggle between death and procreation [J]. A rterioscler Thromb Vasc Biol, 2002, 22 (9): 1370-1380.
[17] Porn-AresM I, Saido T C, Andersson T, et al. Oxidized LDL induces calpain-dependent cell death and ubiquitina-tion of caspase 3 in HMEC-1endothelial cells [J]. Biohem J, 2003,374(2):403-411.
[18] Jiang Y, Zhang J, Xiong J, et al. Ligands of Peroxisome Proliferator-activated Receptor inhibit Homocysteine-induced DNA Methylation of Inducible Nitric Oxide Synthase Gene[J]. Acta Biochim Biophys Sin(Shanghai), 2007, 39(5):366-376.
[19] Naseem KM. The role of nitric oxide in cardiovasculardiseases[J]. Mol Aspects Med, 2005, 26(1):33-65.
[20]何翠瑶,李晓辉,李淑惠,等.三七皂苷对氧化低密度脂蛋白损伤血管内皮细胞保护作用的研究[J].中国药房, 2008,19(6):401-403.
[21] Millette E, Rauch BH, Defawe O, et al. Platelet-derived growth factor-BB-induced human smooth muscle cell proliferation depends on basic FGF release and FGFR-1 activation[J]. Circ Res, 2005, 96(2): 172-179.
[22] Vindis C, Escargueil-Blanc I, Uchida K, et al.Lipid oxidation products and oxidized low-density lipoproteins impair platelet-derived growth factor receptor activity in smooth muscle cells: implication in atherosclerosis[J]. Redox Rep, 2007, 12(1):96-100.
[23] Akishima Y, Akasaka Y, Ishikawa Y, et al. Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development[J]. Mod Pathol,2005,18(3):365-373.
[24] Lupo G, Nicotra A, Giurdanella G, et al. Activation of phospholipase A(2) and MAP kinases by oxidized low-density lipoproteins in immortalized GP8. 39 endothelial cells[J].B iochim B iophys Ac-ta, 2005,1735(2):135-50.
[25] Shibata Y, Kume N, Arai H, et al. Mulberry leaf aqueous fractions inhibit TNF-alphainduced nuclear factor kappaB (NF-kappaB) activation and lectinlike oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells[J]. Atherosclerosis, 2007,193(1):20-27.
[26] Ruan XZ, Moorhead JF, Tao JL, et al. Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines[J]. Arterioscler Thromb Vasc Biol, 2006,26(5):1150-1155.
[27] Kaneyuki U, Ueda S, Yamagishi S, et al. Pitavastatin inhibits lysophosphatidic acid-induced pro-liferation and monocyte chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing Rac-1-mediated reactive oxygen species generation[J].Vascul Pharmacol, 2007, 46(4): 286-292.
[28]张清华,赖晓辉,蒋知新.血管内皮细胞功能与氧化低密度脂蛋白的影响[J].中国组织工程研究与临床康复, 2007,11(6):1174-1176.
[29] Dotevall A , Hult he J ,Rosengren A ,et al . Autoantibodies against oxidized low density lipoprotein and C - reactive protein are associated wit h diabetes and myocardial infarction in women[J].Clin Sci (lond) ,2001,101(5):523–531.
[30] Mironova MA,Klein RL,Virella GT,et al.Anti–modified LDL antibodies LDL-containing immunance complexes and susceptibility of LDL to in vitro oxidation in patients with Type-diabetes[J]. Diabetes, 2000,49(6) :1033–1041.
[31] Raitakari OT ,Pit kanen OP ,Lehtimaki T,et al . Autoantibody against oxidized LDL and LDL article size : relationships to coronary reactivity in young men [J] . J Am Coll Cardiol,1997,30(11):97–102.
[32] Naghavi M ,Libbey P ,Falk E ,et al . Form vulnerable plaque to vulnerable patient a call for new definitions and risk assessment st- rategies : PartⅠ[J]. Circulation, 2003,108(14) : 1664 -1672.
[1] Liuzzo G. Atherosclerosis-an inflammatory disease[J]. N Engl J Med. 2001,26(4):221–230.
[2] Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis[J]. Arterioscler Thromb Vasc Biol. 2007, 27(11):2292–301.
[3] Cybulsky MI, Iiyama K, Li H, Zhu S, Chen M, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis[J]. J Clin Invest. 2001,107(13):1255–62.
[4] Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques[J]. J Clin Invest. 2007,117(1)185–94.
[5] Swirski FK, Libby P, Aikawa E, Alcaide P, Luscinskas FW, et al. Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata[J]. J Clin Invest. 2007,117(1):195–205.
[6] Saederup N, Chan L, Lira SA, Charo IF. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2?/? mice: evidence for independent chemokine functions in atherogenesis[J]. Circulation. 2008,117(13):1642–48.
[7] Mantovani A, Sica A, Locati M. Macrophage polarization comes of age[J]. Immunity. 2005,23(4):344–46.
[8] Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, et al. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice[J]. J Clin Invest. 2000,105(8):1049–56.
[9] Moore KJ, Kunjathoor VV, Koehn SL, Manning JJ, Tseng AA, et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice[J]. J Clin Invest. 2005,115(8):2192–201.
[10] Stoneman V, Braganza D, Figg N, Mercer J, Lang R, et al. Monocyte/macrophage suppression in CD11b diphtheria toxin receptor transgenic mice differentially affects atherogenesis and established plaques[J]. Circ Res. 2007,100(6):884–93.
[11] Byrne GI, Kalayoglu MV. Chlamydia pneumoniae and atherosclerosis: links to the disease proces[sJ]. Am Heart J. 1999,138(5):S488–S490.
[12] Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency[J]. Arterioscler Thromb Vasc Biol. 2005,25(11):2255–64.
[13] Wang Z, Liu B, Wang P, Dong X, Fernandez-Hernando C, et al. Phospholipase Cβ3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice[J]. J Clin Invest. 2008,118(1):195–204.
[14] Makowski L, Boord JB, Maeda K, Babaev VR, Uysal KT, et al. Lack of macrophage fatty- acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis[J]. Nat Med. 2001,7(6):699–705.
[15] Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, et al. Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice[J]. J Clin Invest. 2007,117(12):3900–8.
[16] Zhao B, Song J, Chow WN, St Clair RW, Rudel LL, Ghosh S. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr?/? mice[J]. J Clin Invest. 2007,117(10):2983–92.
[17]林蓉,甘伟杰.药物治疗动脉粥样硬化新途径-抗炎作用[ J ].中国药理学通报, 2004, 20 (5): 499-502.
[18] Erbel C, Sato K, Meyer FB, Kopecky SL, Frye RL, et al. Functional profile of activated dendritic cells in unstable atherosclerotic plaque[J]. Basic Res Cardiol. 2007,102(2):123–32.
[19] Perrin-Cocon L, Coutant F, Agaugue S, Deforges S, Andre P, Lotteau V. Oxidized low-density lipoprotein promotes mature dendritic cell transition from differentiating monocyte[J]. J Immunol. 2001,167(7):3785–91.
[20] Maffia P, Zinselmeyer BH, Ialenti A, Kennedy S, Baker AH, et al. Images in cardiovascular medicine. Multiphoton microscopy for 3-dimensional imaging of lymphocyte recruitment into apolipoprotein-E- deficient mouse carotid artery[J]. Circulation. 2007,115(11):326–28.
[21] Zhou X, Paulsson G, Stemme S, Hansson GK. Hypercholesterolemia is associated with a T helper (Th) 1/Th2 switch of the autoimmune response in atherosclerotic apo E-knockout mice. [J] J Clin Invest. 1998,101(8):1717–25.
[22] Whitman SC, Ramsamy TA. Participatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studies[J]. Can J Physiol Pharmacol. 2006,84(1):67–75.
[23] Lindstedt KA, Mayranpaa MI, Kovanen PT. Mast cells in vulnerable atherosclerotic plaques-a view to a kill[J]. J Cell Mol Med. 2007,11(4):739–58.
[24] Lee M, Calabresi L, Chiesa G, Franceschini G, Kovanen PT. Mast cell chymase degrades apoE and apoA-II in apoA-I-knockout mouse plasma and reduces its ability to promote cellular cholesterol efflux[J]. Arterioscler Thromb Vasc Biol. 2002,22(9):1475–81.
[25] Sun J, Sukhova GK, Wolters PJ, Yang M, Kitamoto S, et al. Mast cells promote atherosclerosis by releasing proinflammatory cytokines[J]. Nat Med. 2007,13(6):719–24.
[26] Caligiuri G, Nicoletti A, Poirier B, Hansson GK. Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice[J]. J Clin Invest. 2002,109(6):745–53.
[27] Zernecke A, Bot I, Djalali-Talab Y, Shagdarsuren E, Bidzhekov K, et al. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis[J]. Circ Res. 2008,102(2):209–17.
[28] von Hundelshausen P, Weber C. Platelets as immune cells: bridging inflammation and cardiovascular disease[J]. Circ Res. 2007,100(1):27–40.
[29] Burger PC, Wagner DD. Platelet P-selectin facilitates atherosclerotic lesion development[J]. Blood. 2003,101(7):2661–66.
[30] Huo Y, Schober A, Forlow SB, Smith DF, Hyman MC, et al. Circulating activated platelets exacerbate atherosclerosis in mice deficient in apolipoprotein E[J]. Nat Med. 2003;9(1):61–67.
[31] Langer HF, Daub K, Braun G, Schonberger T, May AE, et al. Platelets recruit human dendritic cells via Mac-1/JAM-C interaction and modulate dendritic cell function in vitro[J]. Arterioscler Thromb Vasc Biol. 2007,27(6):1463–70.
[32] Schulz C, Schafer A, Stolla M, Kerstan S, Lorenz M, et al. Chemokine fractalkine mediates leukocyte recruitment to inflammatory endothelial cells in flowing whole blood: a critical role for P-selectin expressed on activated platelets[J]. Circulation. 2007,116(7):764–73.
[33] Tedgui A, Mallat Z. Cytokines in atherosclerosis: pathogenic and regulatory pathways[J]. Physiol Rev. 2006,86(2):515–81.
[34] Newby AC. Dual role of matrix metalloproteinases (matrixins) in intimal thickening and athero- sclerotic plaque rupture[J]. Physiol Rev. 2005,85(1):1–31.
[35] Moreno PR, Purushothaman KR, Sirol M, Levy AP, Fuster V. Neovascularization in human athero-sclerosis[J]. Circulation. 2006,113(11):2245–52.
[36] Tsou CL, Peters W, Si Y, Slaymaker S, Aslanian AM, et al. Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites[J]. J Clin Invest. 2007,117(4):902–9.
[37] Gosling J, Slaymaker S, Gu L, Tseng S, Zlot CH, et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B [ J ] . J Clin Invest. 1999,103(6):773–78.
[38] Yu G, Rux AH, Ma P, Bdeir K, Sachais BS. Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-κB-dependent manner[J]. Blood. 2005,105(9):3545–51.
[39] Kuziel WA, Dawson TC, Quinones M, Garavito E, Chenaux G, et al. CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice[J]. Atherosclerosis. 2003,167(1):25–32.
[40] Braunersreuther V, Zernecke A, Arnaud C, Liehn EA, Steffens S, et al. Ccr5 but not Ccr1 deficiency reduces development of diet-induced atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol. 2007,27(2):373–79.
[41] Huo Y, Weber C, Forlow SB, Sperandio M, Thatte J, et al. The chemokine KC, but not monocyte chemoattractant protein-1, triggers monocyte arrest on early atherosclerotic endothelium[J]. J Clin Invest. 2001,108(9):1307–14.
[42] Cheng C, Tempel D, van HR, de Boer HC, Segers D, et al. Shear stress-induced changes in athero- sclerotic plaque composition are modulated by chemokines[J]. J Clin Invest.2007,117(3):616–26.
[43] Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, et al. MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment[J]. Nat Med. 2007, 13(5):587–96.
[44] Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, et al. Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice[J]. Circulation. 2004,109(25):3149-53.
[45] Kraaijeveld AO, de Jager SC, van Berkel TJ, Biessen EA, Jukema JW. Chemokines and atherosclerotic plaque progression: towards therapeutic targeting? [J ] . Curr Pharm Des. 2007,13(10):1039–52.
[46] Aslanian AM, Charo IF. Targeted disruption of the scavenger receptor and chemokine CXCL16 accelerates atherosclerosis[J]. Circulation. 2006,114(6):583-90.
[47] Galkina E, Harry BL, Ludwig A, Liehn EA, Sanders JM, et al. CXCR6 promotes atherosclerosis by supporting T-cell homing, interferon-γproduction, and macrophage accumulation in the aortic wall[J]. Circulation. 2007,116(16):1801–11.
[1]温进坤,韩梅,杜玮南,等.一种快速建立大鼠动脉粥样硬化模型的实验方法[J].中国老年学杂志,2001,21(1) : 50-52.
[2]金晓明,李玉林,唐建武,等.病理学[M].第六版.北京:人民卫生出版社,2008.130.
[3]吴开云,高摄渊,袁融,等.维生素D诱发大鼠动脉粥样硬化的实验研究[J].解剖学报,1996, 27(2): 133-135.
[4]雷大洲,韩清华.TC/HDL-C比值在冠心病诊断中的应用[J].中西医结合心血管病杂志,2009,63(2):63-65.
[5]曲勇,王伟玲,廖琳.ARB降压改善胰岛素敏感性的研究[J].实用糖尿病杂志,2006,2(5):17-18.
[6]王兆宏,陈还珍,李晓英,等.坎地沙坦西酯治疗高血压合并糖代谢异常病人临床研究[J].中西医结合心脑血管病杂志,2008,6(1) :16-18.
[7] Davis BN,Hilyard AC,Nguyen PH,et al. Induction of microRNA- 221 by platelet-derived growth factor signaling is critical formodulation of vascular smooth muscle phenotype [J]. J Biol Chem,2009 284(6): 3728-3738.
[8]李薇,杜军保.动脉粥样硬化发病机制研究进展[J].实用儿科临床杂志, 2009,24(1):58-60.
[9]黄书攀,陈坤赞.坎地沙坦西酯治疗原发性高血压的疗效及对心血管重构的影响[J].全科医学临床与教育,2008,6(2):112.
[10] Suzuki J, Iwai M, Horiuchi M et al. Role of angiotensin II regulated apoptosis through distinct AT1 and AT2 receptors in neointimal formation[J]. Circulation, 2002, 106(7):847-853.
[11] Okumura M, Iwai M, Horiuchi M. Sex difference in vascular injury and the vasoprotective effect of valsartan are related to differential AT2 receptor expression[J].Hypertension, 2005,46(3) 577-583.
[1]朱宝亮,葛顺,刘霞.氧化应激与动脉粥样硬化研究进展[ J].济宁医学院学报,2009,32(5):373-375.
[2] ShinMH,MoonYJ,Seo JE, eta.l Reactive oxygen species produced by NADPH oxidase, xanthine oxidase, andmitochondrialelectron transportsystem mediate heat shock-induced MMP-1 and MMP-9 expression [ J]. FreeRadicBiolMed,2008,44(4): 635-645.
[3]朱晔斌,吴双,孔麟麟,等.氧化型低密度脂蛋白的形成及其致动脉粥样硬化的机制[J].武警医学院学报,2009,18(11):62-64.
[4]李震霄,邹洪梅.氧化应激促进动脉粥样硬化机制研究进展[J].中国动脉硬化杂志,2009, 17(8):702-705.
[5] MadamanchiNR,RungeMS.Mitochondrial dysfunction in atherosclerosis [J].CircRes,2007,100(4): 460-473.
[6] Roucou X, Antonsson B, Martinou JC.Involvement of mitochondria inapoptosis[J].CardiolClin, 2001,19(1): 45-55.
[7] Cai H, Harrison D G. Endothelial dysfunction in cardiovascular disease: the role of oxidant stress[ J ]. Circ Res, 2000, 87(8): 840 - 844.
[8] Kolodgie F D, Gold H K, Burke A P, et al. Intraplaque Hemorrhage and Progression of Coronary Atheroma [ J ].N Engl J Med, 2003, 349(24): 2285-2287.
[9] Sowers J R. Hypertension, angiotensinⅡ, and oxidative stress[J]. N Engl J Med, 2002, 346(3): 1999 - 2001.
[10] McCormickML,Gavrila D,Weintraub NL. Role of oxidative stress in the pathogenesis of abdominal aortic aneuysms[ J ]. Arterioscler Thromb Vasc Biol, 2007,27 (3) : 461-469.
[11] Matsuura E, Kobayashi K, TabuchiM, et al. Oxidative modification of low density lipoprotein and immune regulation of atherosclerosis [ J ]. Prog Lipid Res,2006, 45 (6) : 466-486.
[12] OgawaS,Mori T, Nako K, et al. AngiotensinⅡtype 1 receptor blockers reduce urinary oxidative stressmarkers in hypertensive diabetic nephropathy[ J ]. Hypertension, 2006, 47 (4) : 699 - 705.
[13]林桦.血管紧张素Ⅱ1型受体拮抗剂坎地沙坦的研究进展[ J ].海峡药学,2009,21 (10):9-12.
[14] Mehta JK, Chen J, Hermonat P L,et al. Lectinlike oxidized low- density lipoprotein receptor-1 (LOX-1):A critical player in the development of atherosclerosis and related disorders[J]. Cardiovasc Res,2006,69(1):36-45.
[15] Ma JL,Yang PY,Rui YC,et al. Hemin modulates cytokine expressions in macrophage-derived foam cells via heme oxygenase-1 induction[J]. J Pharmacol Sci,2007,10(3):261-266.
[16]何翠瑶,李晓辉,李淑惠,等.三七皂苷对氧化低密度脂蛋白损伤血管内皮细胞保护作用的研究[J].中国药房, 2008,19(6):401-403.
[17] Berry C,Hamiton CA,Brosnan MJ,et al.Investigation into the source of Super-oxide in human blood vessels:angiotensinⅡincrease superoxide production in human internal mammary arteries[J]. Circulation, 2000,101(3):2206-2212.
[18] Limor R,Kaplan M,Sawamura T,et al.AngiotensinⅡincrease the expression of lectin-like oxidized low-density lipoprotein receptor-1 in human vascular smooth muscle cells via a lipoxygenase-dependent pathway[J].Am J Hypertens,2005,18(3):299-307.
[19] Galle J,Mameghani A,Bolz SS,et al.Oxidized LDL and its compound lysophosphatidylcholine potentiate AngⅡ-induced vasoconstiction by stimulation of RhoA[J].J Am Soc Nephrol,2003,14(6): 1471-1479.
[20] Urata H,Nishimura H,Ganten D.Chymase-dependent angiotensinⅡforming system in humans[J].Am J Hypertens,1996,9(3):277-284.
[1]张伟丽,惠汝太.VEGF及其受体在动脉粥样硬化中的作用[J].中国分子心脏病学杂志,2005,2(5):568-573.
[2] RamosMA, Kuzuya M, Esaki T, et al.Induction of macrophage VEGF in response to oxidized LDL and VEGFaccumulation in human atherosclerotic lesions.ArteriosclerThromb Vasc Biol, 1998,18(7):1 188-1196.
[3]赵瑾,迟路湘,陈德英.基质金属蛋白酶-2在兔颈动脉内膜损伤后动脉粥样硬化斑块中的表达[J].第三军医大学学报,2006,28(8):792-794.
[4]卢维晟,王一尘. MMP22表达与大鼠动脉粥样硬化和血管钙化的关系及辛伐他汀对其影响[J].心脏杂志,2006,18(4):376-378.
[5] Jahnson JL,Baker AH,Oka K,et al.Suppression of atherosclerotic plaque progression and instability by tissue inhibitor of metalloproteinase-2[J].Circulation,2006,113(20):2435-2444.
[6] Luchtefeld M,Grote K,Grothusen C,et al.Angiotensin II induces MMP-2 in p47phox-dependent manner[J]. Biochem Biophys Res Commun,2005,328(1):183-188.
[7] Guo RW,Yang LX,Wang H,et al.Angiotensin II induces matrix metalloproteinase-9 expression via a nuclear factor-kappaB-dependent pathway in vascular smooth muscle cells[J].Regul Pept,2008, 147(13):37-44.
[8] Xie TX,Wei D,Liu M,et al.Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis[J].Oncogene,2004,23(20):3550-3560.
[9] Raymond L,Eck S,Mollmark J,et al.Interleukin-1 beta induction of matrix metalloproteinase-1 transcription in chondrocytes requires ERK-dependent activation of CCAAT enhancer-binding protein-beta[J].J Cell Physiol,2006, 207(3):683-688.
[10] Celletti FL,Waugh JM,Amabile PG,et al.Vascular endothelial growth factor enhances atherosclerotic plaque progression[J].Nat Med,2001,7(4):425-429.