CD36在高脂饮食糖尿病大鼠和2型糖尿病患者中的表达
|
摘要
[目的]研究清道夫受体CD36在高脂饮食糖尿病大鼠和2型糖尿病患者中的表达及其可能的机制,观察噻唑烷二酮类药物—罗格列酮的干预作用。
[方法]SD大鼠高脂饲料喂养4周后,一次性腹腔注射链脲佐菌素35mg/kg体重制备2型糖尿病大鼠模型。采用流式细胞术测定高脂饮食糖尿病大鼠和2型糖尿病患者外周血单核细胞CD36表达的平均荧光强度(MFI),实时定量逆转录酶聚合酶链反应(RT-PCR)法测定高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36mRNA、过氧化物酶体增殖物激活受体γ(PPARγ)mRNA和葡萄糖转运蛋白4(GLUT4)mRNA的表达,Westen blot法测定高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36蛋白质、PPARγ蛋白质和GLUT4蛋白质的表达;并观察罗格列酮干预治疗后上述表达的变化。分析CD36的表达与PPARγ、GLUT4的表达及其它细胞因子、代谢指标间的关系。
[结果](1)高脂饮食一次性腹腔注射链脲佐菌素SD大鼠出现明显的高血糖、高胰岛素血症、脂代谢紊乱和体重增加,与人类2型糖尿病代谢紊乱极为相似。
(2)与正常饮食对照组比较,高脂饮食糖尿病大鼠外周血单核细胞CD36表达的MFI明显升高(P＜0.01);罗格列酮干预后糖尿病大鼠外周血单核细胞CD36表达的MFI与糖尿病组、干预前相比均显著降低(P＜0.01);高脂饮食糖尿病大鼠外周血单核细胞CD36表达的MFI与空腹血糖(FBG)、稳态模型评估胰岛素抵抗指数(HOMA-IR)呈正相关。
(3)与正常饮食对照组比较,高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36mRNA、PPARγmRNA和蛋白质的表达均显著升高(P＜0.01),上述组织中GLUT4 mRNA和蛋白质的表达显著降低(P＜0.01);CD36mRNA及其蛋白质的表达与PPARγmRNA及其蛋白质的表达变化相一致;与高脂饮食糖尿病大鼠比较,罗格列酮干预组糖尿病大鼠骨骼肌组织中CD36、PPARγmRNA及其蛋白质的表达均明显下降(P＜0.05)、GLUT4mRNA及其蛋白质的表达明显上升(P＜0.01),皮下脂肪和附睾脂肪组织CD36、PPARγ和GLUT4 mRNA及其蛋白质的表达均升高,但仅在附睾脂肪组织的变化有统计学意义(P＜0.05)。
(4)2型糖尿病患者外周血单核细胞CD36表达的MFI较正常对照者明显增高(P＜0.01),伴有动脉粥样硬化的患者明显高于无动脉粥样硬化患者(P＜0.01),单核细胞CD36表达的MFI与糖尿病病程、FBG、HbAlc、HOMA-IR呈正相关。
(5)与对照组以及治疗前比较,2型糖尿病患者罗格列酮治疗后单核细胞CD36表达的MFI显著下降(P＜0.01),血清可溶性血管细胞粘附分子-1(sVCAM-1)、肿瘤坏死因子α(TNFα)水平明显降低(P＜0.01),血清脂联素水平明显升高(P＜0.01);单核细胞CD36表达的MFI与血清sVCAM-1、TNFα水平呈正相关、与血清脂联素水平呈负相关。
[结论]高脂饮食、一次性腹腔注射链脲佐菌素SD大鼠是比较理想的2型糖尿病动物模型;2型糖尿病状态下外周血单核细胞CD36表达增加,可能是促进糖尿病动脉粥样硬化的机制之一,高血糖、胰岛素抵抗是单核细胞CD36表达的主要上调因子;罗格列酮能降低2型糖尿病外周血单核细胞CD36表达,其机制可能在于降低血糖、减轻氧化应激、改善胰岛素抵抗和减轻炎症反应;CD36在糖尿病大鼠骨骼肌、脂肪组织的表达受PPARγ的调节并具有组织特异性;皮下脂肪和附睾脂肪组织在胰岛素抵抗、脂质代谢、动脉粥样硬化中可能起不同的作用。
Objective:To investigate the expression of scavenger receptor CD36 in High-Fat-Diet induced diabetic rats and Type 2 diabetes and the possible mechanism, and to observe the effects of thiazolidinediones—rosiglitazone intervention.
Method:Type 2 diabetic rat models were induced by High-Fat-Diet SD rats combined with intraperitoneal injection streptozotocin(STZ) 35mg/kg once.The expression of CD36 in monocytes from High-Fat-Diet induced diabetic rats and Type 2 diabetes were measured before and after rosiglitazone intervention by laser flow cytometry.Expressions of CD36 mRNA,Peroxisome proliferator-activated receptorγ(PPARγ) mRNA,Glucose transporter 4(GLUT4) mRNA and their protein in skeletal muscle,subcutaneous adipose tissue and epididymal adipose tissue from High-Fat-Diet induced diabetic rats were investigated before and after rosiglitazone intervention by real time RT-PCR and Western blot analysis respectively.Assay the correlation between monocytes CD36 expression and PPARγ、GLUT4 and other cytokines,metabolic parameters.
Results:(1) Similar to Type 2 diabetes metabolic disorder,High-Fat-Diet combined intraperitoneal injection STZ once SD rats appeared evident hyperglycemia,hyperinsulinemia,lipid metabolic disorder and body weight gain.
(2) Flow cytometry showed that the MFI of monocytes CD36 expressions in diabetic rats were significantly higher in comparison with controls(P＜0.01).After rosiglitazone intervention the MFI of monocytes CD36 expressions were significantly decreased(P＜0.01).There was a positive correlation between monocytes CD36 MFI and FBG、HOMA-IR.
(3) Expressions of CD36 mRNA,PPARγmRNA and their protein in skeletal muscle, subcutaneous adipose tissue and epididymal adipose tissue from diabetic rats were significantly increased and expressions of GLUT4 mRNA and protein in above-mentioned tissues were significantly decreased(P＜0.01).There was a coincidence change between expressions of CD36 and PPARγmRNA or protein. After rosiglitazone intervention,expressions of CD36mRNA,PPARγmRNA and their protein in skeletal muscle were significantly decreased(P＜0.05),expressions of GLUT4 mRNA and protein in skeletal muscle were significantly increased (P＜0.01).Expressions of CD36mRNA,PPARγmRNA,GLUT4 mRNA and their protein in subcutaneous adipose tissue and epididymal adipose tissue were all increased but only in epididymal adipose tissue there was a statistics significance (P＜0.05).
(4) The MFI of monocytes CD36 expressions were significantly higher in Type 2 diabetes in comparison with healthy controls(P＜0.01).The MFI of monocytes CD36 expressions in atherosclerosis diabetes were significantly higher in comparison with nonatherosclerosis diabetes(P＜0.01).There was a positive correlation between monocytes CD36 MFI and diabetes duration、FBG、HbA1_C、HOMA-IR.
(5) After rosiglitazone intervention,the MFI of monocytes CD36 expressions were significantly decreased in comparison with controls and before rosiglitazone intervention(P＜0.01).The serum levels of sVCAM-1 and TNFαwere significantly decreased(P＜0.01) and the serum levels of adiponectin were significantly increased (P＜0.01).There was a positive correlation between monocytes CD36 MFI and serum levels of sVCAM-1 and TNFα,a inverse correlation between monocytes CD36 MFI and serum levels of adiponectin.
Conclusion:High-Fat-Diet combined intraperitoneal injection STZ once SD rats were good Type 2 diabetic rat models.The increased expression of scavenger receptor CD36 in monocytes in the condition of Type 2 diabetes may be one of the mechanism of accelerated atherosclerosis in diabetic,hyperglycemia and insulin resistance were the main up-regulation factors.Rosiglitazone could reduce CD36 expression in monocytes,the mechanism might lie in the good glycaemic control,relief of oxidative stress,improvement of insulin resistance and relief of inflammatory reaction.The expression of CD36 in rat skeletal muscle and adipose tissue was regulated by PPARγand exist tissue specificity.There may be exist different mechanism between subcutaneous adipose tissue and epididymal visceral adipose tissue in insulin resistance,metabolism of lipid and atherosclerosis.
[方法]SD大鼠高脂饲料喂养4周后,一次性腹腔注射链脲佐菌素35mg/kg体重制备2型糖尿病大鼠模型。采用流式细胞术测定高脂饮食糖尿病大鼠和2型糖尿病患者外周血单核细胞CD36表达的平均荧光强度(MFI),实时定量逆转录酶聚合酶链反应(RT-PCR)法测定高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36mRNA、过氧化物酶体增殖物激活受体γ(PPARγ)mRNA和葡萄糖转运蛋白4(GLUT4)mRNA的表达,Westen blot法测定高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36蛋白质、PPARγ蛋白质和GLUT4蛋白质的表达;并观察罗格列酮干预治疗后上述表达的变化。分析CD36的表达与PPARγ、GLUT4的表达及其它细胞因子、代谢指标间的关系。
[结果](1)高脂饮食一次性腹腔注射链脲佐菌素SD大鼠出现明显的高血糖、高胰岛素血症、脂代谢紊乱和体重增加,与人类2型糖尿病代谢紊乱极为相似。
(2)与正常饮食对照组比较,高脂饮食糖尿病大鼠外周血单核细胞CD36表达的MFI明显升高(P＜0.01);罗格列酮干预后糖尿病大鼠外周血单核细胞CD36表达的MFI与糖尿病组、干预前相比均显著降低(P＜0.01);高脂饮食糖尿病大鼠外周血单核细胞CD36表达的MFI与空腹血糖(FBG)、稳态模型评估胰岛素抵抗指数(HOMA-IR)呈正相关。
(3)与正常饮食对照组比较,高脂饮食糖尿病大鼠骨骼肌、皮下脂肪、附睾脂肪组织中CD36mRNA、PPARγmRNA和蛋白质的表达均显著升高(P＜0.01),上述组织中GLUT4 mRNA和蛋白质的表达显著降低(P＜0.01);CD36mRNA及其蛋白质的表达与PPARγmRNA及其蛋白质的表达变化相一致;与高脂饮食糖尿病大鼠比较,罗格列酮干预组糖尿病大鼠骨骼肌组织中CD36、PPARγmRNA及其蛋白质的表达均明显下降(P＜0.05)、GLUT4mRNA及其蛋白质的表达明显上升(P＜0.01),皮下脂肪和附睾脂肪组织CD36、PPARγ和GLUT4 mRNA及其蛋白质的表达均升高,但仅在附睾脂肪组织的变化有统计学意义(P＜0.05)。
(4)2型糖尿病患者外周血单核细胞CD36表达的MFI较正常对照者明显增高(P＜0.01),伴有动脉粥样硬化的患者明显高于无动脉粥样硬化患者(P＜0.01),单核细胞CD36表达的MFI与糖尿病病程、FBG、HbAlc、HOMA-IR呈正相关。
(5)与对照组以及治疗前比较,2型糖尿病患者罗格列酮治疗后单核细胞CD36表达的MFI显著下降(P＜0.01),血清可溶性血管细胞粘附分子-1(sVCAM-1)、肿瘤坏死因子α(TNFα)水平明显降低(P＜0.01),血清脂联素水平明显升高(P＜0.01);单核细胞CD36表达的MFI与血清sVCAM-1、TNFα水平呈正相关、与血清脂联素水平呈负相关。
[结论]高脂饮食、一次性腹腔注射链脲佐菌素SD大鼠是比较理想的2型糖尿病动物模型;2型糖尿病状态下外周血单核细胞CD36表达增加,可能是促进糖尿病动脉粥样硬化的机制之一,高血糖、胰岛素抵抗是单核细胞CD36表达的主要上调因子;罗格列酮能降低2型糖尿病外周血单核细胞CD36表达,其机制可能在于降低血糖、减轻氧化应激、改善胰岛素抵抗和减轻炎症反应;CD36在糖尿病大鼠骨骼肌、脂肪组织的表达受PPARγ的调节并具有组织特异性;皮下脂肪和附睾脂肪组织在胰岛素抵抗、脂质代谢、动脉粥样硬化中可能起不同的作用。
Objective:To investigate the expression of scavenger receptor CD36 in High-Fat-Diet induced diabetic rats and Type 2 diabetes and the possible mechanism, and to observe the effects of thiazolidinediones—rosiglitazone intervention.
Method:Type 2 diabetic rat models were induced by High-Fat-Diet SD rats combined with intraperitoneal injection streptozotocin(STZ) 35mg/kg once.The expression of CD36 in monocytes from High-Fat-Diet induced diabetic rats and Type 2 diabetes were measured before and after rosiglitazone intervention by laser flow cytometry.Expressions of CD36 mRNA,Peroxisome proliferator-activated receptorγ(PPARγ) mRNA,Glucose transporter 4(GLUT4) mRNA and their protein in skeletal muscle,subcutaneous adipose tissue and epididymal adipose tissue from High-Fat-Diet induced diabetic rats were investigated before and after rosiglitazone intervention by real time RT-PCR and Western blot analysis respectively.Assay the correlation between monocytes CD36 expression and PPARγ、GLUT4 and other cytokines,metabolic parameters.
Results:(1) Similar to Type 2 diabetes metabolic disorder,High-Fat-Diet combined intraperitoneal injection STZ once SD rats appeared evident hyperglycemia,hyperinsulinemia,lipid metabolic disorder and body weight gain.
(2) Flow cytometry showed that the MFI of monocytes CD36 expressions in diabetic rats were significantly higher in comparison with controls(P＜0.01).After rosiglitazone intervention the MFI of monocytes CD36 expressions were significantly decreased(P＜0.01).There was a positive correlation between monocytes CD36 MFI and FBG、HOMA-IR.
(3) Expressions of CD36 mRNA,PPARγmRNA and their protein in skeletal muscle, subcutaneous adipose tissue and epididymal adipose tissue from diabetic rats were significantly increased and expressions of GLUT4 mRNA and protein in above-mentioned tissues were significantly decreased(P＜0.01).There was a coincidence change between expressions of CD36 and PPARγmRNA or protein. After rosiglitazone intervention,expressions of CD36mRNA,PPARγmRNA and their protein in skeletal muscle were significantly decreased(P＜0.05),expressions of GLUT4 mRNA and protein in skeletal muscle were significantly increased (P＜0.01).Expressions of CD36mRNA,PPARγmRNA,GLUT4 mRNA and their protein in subcutaneous adipose tissue and epididymal adipose tissue were all increased but only in epididymal adipose tissue there was a statistics significance (P＜0.05).
(4) The MFI of monocytes CD36 expressions were significantly higher in Type 2 diabetes in comparison with healthy controls(P＜0.01).The MFI of monocytes CD36 expressions in atherosclerosis diabetes were significantly higher in comparison with nonatherosclerosis diabetes(P＜0.01).There was a positive correlation between monocytes CD36 MFI and diabetes duration、FBG、HbA1_C、HOMA-IR.
(5) After rosiglitazone intervention,the MFI of monocytes CD36 expressions were significantly decreased in comparison with controls and before rosiglitazone intervention(P＜0.01).The serum levels of sVCAM-1 and TNFαwere significantly decreased(P＜0.01) and the serum levels of adiponectin were significantly increased (P＜0.01).There was a positive correlation between monocytes CD36 MFI and serum levels of sVCAM-1 and TNFα,a inverse correlation between monocytes CD36 MFI and serum levels of adiponectin.
Conclusion:High-Fat-Diet combined intraperitoneal injection STZ once SD rats were good Type 2 diabetic rat models.The increased expression of scavenger receptor CD36 in monocytes in the condition of Type 2 diabetes may be one of the mechanism of accelerated atherosclerosis in diabetic,hyperglycemia and insulin resistance were the main up-regulation factors.Rosiglitazone could reduce CD36 expression in monocytes,the mechanism might lie in the good glycaemic control,relief of oxidative stress,improvement of insulin resistance and relief of inflammatory reaction.The expression of CD36 in rat skeletal muscle and adipose tissue was regulated by PPARγand exist tissue specificity.There may be exist different mechanism between subcutaneous adipose tissue and epididymal visceral adipose tissue in insulin resistance,metabolism of lipid and atherosclerosis.
引文
1 Wei M, Gaskill SP, Haffner SM, et al. Effect of diabetes and level of glycaemia on all cause and cardiovascular mortality. Diabetes Care 1998;21:1167-1172.
2 Temelkova-Kurktschiev TS, Koehler C, Henkel E, et al. Postchailenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care 2000;23:1830-1834.
3 Adachi H, Tsujimoto M. Endothelial scavenger receptors. Prog Lipid Res 2006.
4 Podrez EA, Febbraio M, Sheibani N, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 2000;105:1095-1108.
5 Huh HY, Pearce SF, Yesner M, et al. Regulated expression of CD36 in foam cell formation. Blood 1996;87:2020-2028.
6 Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem 1999;274:19055-19062.
7 Podrez EA, Poliakov E, Shen Z, et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem 2002;277:38517-38523.
8 Huh HY, Pearce SF, Yesner LM. et al. Regulated expression of CD36 during monocyte to macrophage differentiation: Potential role of CD36 in foam cell formation. Blood 1996;87:2020-2028.
9 Nozaki S, Kashiwagi H, Yamashita S, et al. Reduced uptake of oxidized low density lipoprotein in monocyte-derived macrophages form CD36 deficient subjects. J Clin Invest 1995:96:1859-1865.
10 Moore KJ, Rose ED, Fitzgerald ML, et al. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med 2001;7:41-47.
11 Takahashi Y, Ide T, Diatary n-3 fatty acids affect mRNA level of brown adipose tissue uncoupling protein 1, and white adipose tissue leptin and glucose transporter 4 in the rat. Br J Nutr 2000;84:175-184.
12 Le Roith D, Zick Y. Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care 2001;24:588-597.
13 Reed MJ, Meszaros K, Entes LJ, et al. A new rat model of type 2 diabetes:the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390-1394.
14 UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complication in type 2 diabetes. Br Med J 1998;317:703-713.
15 Holman R. The UKPDS: implications for the dyslipidaemic patient. Avta Diabetol 2001;38 Suppl 1:S9-14.
16 The DECODE Study Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and two-hour diagnostic criteria. Arch Intern Med 2001; 161:397-405.
17 Endemann G, Stanton LW, Madden KS, et al. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993;268:11811-11816.
18 Acton SL, Kozarsky KF, Rigotti A. The HDL receptor SR-BI: a new therapeutic target for atherosclerosis? Mol Med Today 1999;5:518-524.
19 Boullier A, Gillotte KL, Horkko S, et al. The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein. J Biol Chem 2000;275:9163-9169.
20 Acton SL, Scherer PE, Lodish HF, et al. Expression cloning of SR-BI, a CD36 related class B scavenger receptor. J Biol Chem 1994;269:21003-21009.
21 Bornstein P. Thtombospondins as matricellular modulatoes of cell fuction. J Clin Invest 2001;107:929-934.
22 Nakata A, Nakagawa Y, Nishida M. et al.CD36, a novel receptor for oxidized low-density lipoprotein is highly expressed on lipidladen macrophage in human atherosclerotic arota. Arterioscler Thromb Vasc Biol 1999;19:1333-1339.
23 Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med 2001;7:840-845.
24 Sampson MJ, Davies IR, Braschi S, et al. Increased expression of a scavenger receptor(CD36) in monocytes form subjects with type 2 diabetes. Atherosclerosis 2003; 167:129-134.
25 Farhangkhoee H, Khan ZA, Barbin Y, et al. Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction. Diabetologia 2005;48:1401-1410.
26 Ohgami N, Nagai R, Ikemoto M, et al. CD36, serves as a receptor for advanced glycation end products(AGE). J Diabetes Complications 2002; 16: 56-59.
27 Kuniyasu A, Ohgami N, Hayashi S, et al. CD36-mediated endocytic uptake of advanced glycation end products(AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett 2003;537:85-90.
28 Reilly MR Wolfe ML, Rhodes T, et al. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 2004;110:803-809.
29 Handberg A, Levin K, Hojlund K, et al. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006; 114: 1169-1176.
30 Han J, Hajjar DP, Zhou X. et al. Regulation of peroxisome proliferrator-actived receptor-gamma-mediated gene expression. A new mechanism of action for high density lipoprotein. J Biol Chem 2002;277:23582-23586.
31 Han J, Hajjar DP, Tauras JM, et al. Transforing growth factor-β_1(TGFβ_1) and TGFβ_2 decrease expression of CD36, the type B scavenger, through mitogen actived protein kinase phosphorylation of peroxisome proliferrator-actived receptor-gamma. J Biol Chem 2000;275:1241-1246.
32 Chen M,Yang YK,Loux TJ,et al.The role of hyperglycemia in FAT/CD36 expression and function.Pediatr Surg Int 2006;22:647-654.
33 Chabowski A,Chatham JC,Tandon NN,et al.Fatty acid transport and FAT/CD36 are increased in red but not in white skeletal muscle of ZDF rats.Am J Physiol Endocrinol METAB 2006;291:E675-E682.
34 Katz EB,Burcelin R,Tsao TS,et al.The metabolic consequences of altered glucose transporter expression in transgenic mice.Mol Med 1996;74:639-652.
35 宋春宇,毕会民.高脂饮食喂养对大鼠骨骼肌膜GLU4含量的影响.中国病理生理杂志,2004;20:1866-1870.
36 Yonemitsu S,Nishimura H,Shintani M,et al.Troglitazone induces GLUT4 translocation in L6myotubes.Diabetes 2001;50:1093-1101.
37 Chawla A,Boisvert WA,Lee CH.et al.PPAR gamma-LXR-ABCA1 pathway in macrophages is involved cholesterol efflux and atherogenisis.Mol Cell 2001;7:161-171.
38 Oram JF.ATP-binding casstte transporter Al and cholesterol trafficking.Curr Opin Lipidol 2002;13:373-381.
39 Smith AC,Mullen KL,Junkin KA,et al.Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia.Am J Physiol Endocrinol Metab 2007;293:E172-E181.
40 Kim H,Haluzik M,Gavrilova O,et al.Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes.Diabetologia 2004;47:2215-2225.
41 Ryden L,Standl E,Bartnik M,et al.Guidelines on diabetes,pre-diabetes,and cardiovascular diseases:executive summary.The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology(ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007:28:88-136.
42 Lyons TJ. Oxidized low density lipoprotein: a role in the pathosclerosis of atherosclerosis in diabetes. Diabet Med 1991 ;8:411-419.
43 Kopprasch S, Pietzsch J, Kuhlisch E, et al. In vivo evidence for increased oxidation of circulating LDL in impaired glucose tolerance. Diabetes 2002;51:3102-3106.
44 Truman LA, Ogden CA, Howie SE, et al. Macrophage chemotaxis to apoptotic Burkitt's lymphoma cell in vitro: role of CD14 and Cd36. Immunobiology 2004;209:21-30.
45 Reilly MP, Wolfe ML, Rhodes T, et al. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 2004;l 10:803-809.
46 Handberg A, Levin K, Hojlund K, et al. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006; 114: 1169-1176.
47 Pasceri V, Wu HD, Willerson JT, et al. Modulation of vascular inflammationin vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation, 2000,101:235-238.
48 Li AC, Brown KK, Silvestre MJ, et al. Peroxisome proliferator activated receptorγ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin invest 2000;106:523-531.
49 Sidhu JS, Cowan D, Kaski JC, et al. The effects of rosiglitazone, a peroxisome proliferrator-actived receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 2003;42:1757-1763.
50 Alessi MC, Bastelica D, Mavri A, et al. Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol 2003;23:1262-1268.
51 Daynes RA, Jones DC. Emerging role of PPARs in inflammation and immunity. Nat rev Immunol 2002;2:748-759.
52 Eberardt W, Akool el S, Rebhan J. Inhibition of cytokine-induced matrix metalloproteinase 9 expression by peroxisome proliferrator-actived receptor alpha agonists is indirect and due to a NO-mediated reduction of mRNA stability. J Biol Chem 2002;277:33518-33528.
53 Ouchi N, Kihara S, Artia Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001;103:1057-1063.
54 Daimon M, Oizumi T, Saitoh T, et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population-The Funagata study. Diabetes Care 2003;26:2015-2020.
55 Tan GD, Fielding BA, Currie JM, et al. The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 2005;48:83-95.
56 Kin H, Haluzik M, Gavrilova O, et al. Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes. Diabetologia 2004;47:2215-2225.
57 Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinedione on plasma adiponectin levels in normal,obese,and type 2 diabetic subjects. Diabetes 2002;51:2968-2974.
58 Yang WS, Jeng CY, Wu TJ, et al. Synthetic peroxisome proliferators-activated receptor-gama agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 2002;25:376-380.
59 Neschen S, Morino K, Rossbacher JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferators-activated receptor-y-dependent mechanism in mice. Diabetes 2006;55:924-928.
60 Argmann CA, Sawyez CG, McNeil CJ, et al. Activation of peroxisome proliferators-activated receptor gamma and retinoid X receptor results in net depletion of cellular cholesteryl esters in macrophages exposed to oxidized lipoproteins. Arterioscler Thromb Vasc Biol 2003;23:475-482.
61 Chinetti G, Gbaguidi FG, Griglio S, et al. CLS/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferators-activated receptor. Circulation 2000; 101:2411-2417.
62 Ricote M, Li AC, Willson TM, et al. The peroxisome proliferators-activated receptor y is a negative regulator of macrophage activation. Nature 1998;391:79-82.
63 Bodies AM, Varma V, Yao-Borengasser A, et al. Pioglitazone induces apoptosis of macrophages in human adipose tissue. J Lipid Res 2006;47:2080-2088.
1 David R.Recent progress in defining the role of scavenger receptors in lipid transport,atherosclerosis and host defence.Curr opin in Lipid,1998,9:425-432.
2 Febbraio M,Hajjar DP,Silverstein RL.CD36:a class B scavenger receptor involved in angiogenesis,atherosclerosis,inflammation,and lipid metabolism.J Clin Invest,2001,108:785-791.
3 杨向东,李红霞,王抒等.CD36介导氧化型低密度脂蛋白诱导U937细胞泡沫化和凋亡.中国动脉硬化杂志,2000,8:315-318.
4 Nicholson AC,Han J,Febbraio M,et al.Role of CD36,the macrophage class B scavenger receptor,in atherosclerosis.Ann N Y Acad Sci,2001,947(12):224-228.
5 Nagy L,Tontonoz P,Alvarez JG,et al.Oxidized LDL regulates macrophage gene expression through ligiand activation of PPAR-γ.Cell,1998,93(1):229-240.
6 Marx N,Kehrle B,Kohlhammer K,et al.PPAR activators as antiinflammatary mediators in human T lyphocytes:implications for atherosclerosis and translation associated artheriosclerosis.Circres,2002,4,90(6):703-710.
7 Ricote M,Li AC,Willson TM,et al.The peroxisome proliferators activated receptor γ is a negative regulator of macrophage activation.Nature,1998,391(6662):79-82.
8 Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem, 1999, 274:19055-19062.
9 Vidya V, Kunjathoor, Maria Febbraio, et al. Scavenger receptor class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem Vol December,2002, 277,51:49982-49988.
10 Nozaki S, Kashiwagi H, Yamashita S, et al.Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36 deficient subjects. J Clin Invest, 1995,96:1859-1865.
11 Nicholson A, Pearce SFA, Silverstein R. Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site. Arterioscler Thromb, 1995,15:269- 275.
12 Boullier A, Gillotte KL, Horkko S, et al. The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moietied of the lipoprotein. J Biol Chem, 2000,275,9163-9169.
13 Chawla A, Barak Y, Nagy L, et al. PPAR-gamma dependent and independent effents on macrophage-geneexpression in lipoid metabolism and inflammation. Nat Med,2001,7:23-24.
14 Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med,2001,7: 840-846.
15 Nesrin Kartal O zer a, Yesim Negis. Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits. Atherosclerosis, article in press, 2005.
16 Fuhrman B, Koren L, Volkova N, et al. Atorvastatin therapy in hypercholesterolomic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis, 2002,164:179-185.
17 Han J, Zhou X, Yokoyama T, et al. Pitavastatin downregulates expression of the macrophage type Bscavenger receptor, CD36. Circulation, 2004, 17:790-796.
18 Han J, Hajjar DP, Tauras JM, et al. Transforming growth factor-β_1(TGF β_1) and TGF β_2 decrease expression of CD36, the type B scavenger, through mitogen activated protein kinase phosphorylation of peroxisome proliferators activated receptor-gamma. J Biol Chem,2000,275:1241-1246.
19 Moore KJ, Rose ED, Fitzgerald ML, et al. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med,2001,7:41-47.
20 Han J, Hajjar DP, Zhou X, et al. Regulation of peroxisome proliferators-activated receptor-gamma-mediated gene expression. A new mechanism of action for high density lipoprotein. J Biol Chem, 277,2002:23582-23586.
21 CalcoD, Gomez-CoronadoD, SuarezY, et al. Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL and VLDL. J Lipid Res, 1998, 39: 777- 787.
22 Moore KJ. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest, 2005,115:2192-2201.
23 Witztum JL. You are tight too. J Clin Invest,2005,l 15:2072-2075.
2 Temelkova-Kurktschiev TS, Koehler C, Henkel E, et al. Postchailenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care 2000;23:1830-1834.
3 Adachi H, Tsujimoto M. Endothelial scavenger receptors. Prog Lipid Res 2006.
4 Podrez EA, Febbraio M, Sheibani N, et al. Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 2000;105:1095-1108.
5 Huh HY, Pearce SF, Yesner M, et al. Regulated expression of CD36 in foam cell formation. Blood 1996;87:2020-2028.
6 Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem 1999;274:19055-19062.
7 Podrez EA, Poliakov E, Shen Z, et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem 2002;277:38517-38523.
8 Huh HY, Pearce SF, Yesner LM. et al. Regulated expression of CD36 during monocyte to macrophage differentiation: Potential role of CD36 in foam cell formation. Blood 1996;87:2020-2028.
9 Nozaki S, Kashiwagi H, Yamashita S, et al. Reduced uptake of oxidized low density lipoprotein in monocyte-derived macrophages form CD36 deficient subjects. J Clin Invest 1995:96:1859-1865.
10 Moore KJ, Rose ED, Fitzgerald ML, et al. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med 2001;7:41-47.
11 Takahashi Y, Ide T, Diatary n-3 fatty acids affect mRNA level of brown adipose tissue uncoupling protein 1, and white adipose tissue leptin and glucose transporter 4 in the rat. Br J Nutr 2000;84:175-184.
12 Le Roith D, Zick Y. Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care 2001;24:588-597.
13 Reed MJ, Meszaros K, Entes LJ, et al. A new rat model of type 2 diabetes:the fat-fed, streptozotocin-treated rat. Metabolism 2000;49:1390-1394.
14 UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complication in type 2 diabetes. Br Med J 1998;317:703-713.
15 Holman R. The UKPDS: implications for the dyslipidaemic patient. Avta Diabetol 2001;38 Suppl 1:S9-14.
16 The DECODE Study Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and two-hour diagnostic criteria. Arch Intern Med 2001; 161:397-405.
17 Endemann G, Stanton LW, Madden KS, et al. CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993;268:11811-11816.
18 Acton SL, Kozarsky KF, Rigotti A. The HDL receptor SR-BI: a new therapeutic target for atherosclerosis? Mol Med Today 1999;5:518-524.
19 Boullier A, Gillotte KL, Horkko S, et al. The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein. J Biol Chem 2000;275:9163-9169.
20 Acton SL, Scherer PE, Lodish HF, et al. Expression cloning of SR-BI, a CD36 related class B scavenger receptor. J Biol Chem 1994;269:21003-21009.
21 Bornstein P. Thtombospondins as matricellular modulatoes of cell fuction. J Clin Invest 2001;107:929-934.
22 Nakata A, Nakagawa Y, Nishida M. et al.CD36, a novel receptor for oxidized low-density lipoprotein is highly expressed on lipidladen macrophage in human atherosclerotic arota. Arterioscler Thromb Vasc Biol 1999;19:1333-1339.
23 Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med 2001;7:840-845.
24 Sampson MJ, Davies IR, Braschi S, et al. Increased expression of a scavenger receptor(CD36) in monocytes form subjects with type 2 diabetes. Atherosclerosis 2003; 167:129-134.
25 Farhangkhoee H, Khan ZA, Barbin Y, et al. Glucose-induced up-regulation of CD36 mediates oxidative stress and microvascular endothelial cell dysfunction. Diabetologia 2005;48:1401-1410.
26 Ohgami N, Nagai R, Ikemoto M, et al. CD36, serves as a receptor for advanced glycation end products(AGE). J Diabetes Complications 2002; 16: 56-59.
27 Kuniyasu A, Ohgami N, Hayashi S, et al. CD36-mediated endocytic uptake of advanced glycation end products(AGE) in mouse 3T3-L1 and human subcutaneous adipocytes. FEBS Lett 2003;537:85-90.
28 Reilly MR Wolfe ML, Rhodes T, et al. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 2004;110:803-809.
29 Handberg A, Levin K, Hojlund K, et al. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006; 114: 1169-1176.
30 Han J, Hajjar DP, Zhou X. et al. Regulation of peroxisome proliferrator-actived receptor-gamma-mediated gene expression. A new mechanism of action for high density lipoprotein. J Biol Chem 2002;277:23582-23586.
31 Han J, Hajjar DP, Tauras JM, et al. Transforing growth factor-β_1(TGFβ_1) and TGFβ_2 decrease expression of CD36, the type B scavenger, through mitogen actived protein kinase phosphorylation of peroxisome proliferrator-actived receptor-gamma. J Biol Chem 2000;275:1241-1246.
32 Chen M,Yang YK,Loux TJ,et al.The role of hyperglycemia in FAT/CD36 expression and function.Pediatr Surg Int 2006;22:647-654.
33 Chabowski A,Chatham JC,Tandon NN,et al.Fatty acid transport and FAT/CD36 are increased in red but not in white skeletal muscle of ZDF rats.Am J Physiol Endocrinol METAB 2006;291:E675-E682.
34 Katz EB,Burcelin R,Tsao TS,et al.The metabolic consequences of altered glucose transporter expression in transgenic mice.Mol Med 1996;74:639-652.
35 宋春宇,毕会民.高脂饮食喂养对大鼠骨骼肌膜GLU4含量的影响.中国病理生理杂志,2004;20:1866-1870.
36 Yonemitsu S,Nishimura H,Shintani M,et al.Troglitazone induces GLUT4 translocation in L6myotubes.Diabetes 2001;50:1093-1101.
37 Chawla A,Boisvert WA,Lee CH.et al.PPAR gamma-LXR-ABCA1 pathway in macrophages is involved cholesterol efflux and atherogenisis.Mol Cell 2001;7:161-171.
38 Oram JF.ATP-binding casstte transporter Al and cholesterol trafficking.Curr Opin Lipidol 2002;13:373-381.
39 Smith AC,Mullen KL,Junkin KA,et al.Metformin and exercise reduce muscle FAT/CD36 and lipid accumulation and blunt the progression of high-fat diet-induced hyperglycemia.Am J Physiol Endocrinol Metab 2007;293:E172-E181.
40 Kim H,Haluzik M,Gavrilova O,et al.Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes.Diabetologia 2004;47:2215-2225.
41 Ryden L,Standl E,Bartnik M,et al.Guidelines on diabetes,pre-diabetes,and cardiovascular diseases:executive summary.The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology(ESC) and of the European Association for the Study of Diabetes (EASD). Eur Heart J 2007:28:88-136.
42 Lyons TJ. Oxidized low density lipoprotein: a role in the pathosclerosis of atherosclerosis in diabetes. Diabet Med 1991 ;8:411-419.
43 Kopprasch S, Pietzsch J, Kuhlisch E, et al. In vivo evidence for increased oxidation of circulating LDL in impaired glucose tolerance. Diabetes 2002;51:3102-3106.
44 Truman LA, Ogden CA, Howie SE, et al. Macrophage chemotaxis to apoptotic Burkitt's lymphoma cell in vitro: role of CD14 and Cd36. Immunobiology 2004;209:21-30.
45 Reilly MP, Wolfe ML, Rhodes T, et al. Measures of insulin resistance add incremental value to the clinical diagnosis of metabolic syndrome in association with coronary atherosclerosis. Circulation 2004;l 10:803-809.
46 Handberg A, Levin K, Hojlund K, et al. Identification of the oxidized low-density lipoprotein scavenger receptor CD36 in plasma: a novel marker of insulin resistance. Circulation 2006; 114: 1169-1176.
47 Pasceri V, Wu HD, Willerson JT, et al. Modulation of vascular inflammationin vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation, 2000,101:235-238.
48 Li AC, Brown KK, Silvestre MJ, et al. Peroxisome proliferator activated receptorγ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin invest 2000;106:523-531.
49 Sidhu JS, Cowan D, Kaski JC, et al. The effects of rosiglitazone, a peroxisome proliferrator-actived receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients. J Am Coll Cardiol 2003;42:1757-1763.
50 Alessi MC, Bastelica D, Mavri A, et al. Plasma PAI-1 levels are more strongly related to liver steatosis than to adipose tissue accumulation. Arterioscler Thromb Vasc Biol 2003;23:1262-1268.
51 Daynes RA, Jones DC. Emerging role of PPARs in inflammation and immunity. Nat rev Immunol 2002;2:748-759.
52 Eberardt W, Akool el S, Rebhan J. Inhibition of cytokine-induced matrix metalloproteinase 9 expression by peroxisome proliferrator-actived receptor alpha agonists is indirect and due to a NO-mediated reduction of mRNA stability. J Biol Chem 2002;277:33518-33528.
53 Ouchi N, Kihara S, Artia Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001;103:1057-1063.
54 Daimon M, Oizumi T, Saitoh T, et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population-The Funagata study. Diabetes Care 2003;26:2015-2020.
55 Tan GD, Fielding BA, Currie JM, et al. The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes. Diabetologia 2005;48:83-95.
56 Kin H, Haluzik M, Gavrilova O, et al. Thiazolidinediones improve insulin sensitivity in adipose tissue and reduce the hyperlipidaemia without affecting the hyperglycaemia in a transgenic model of type 2 diabetes. Diabetologia 2004;47:2215-2225.
57 Yu JG, Javorschi S, Hevener AL, et al. The effect of thiazolidinedione on plasma adiponectin levels in normal,obese,and type 2 diabetic subjects. Diabetes 2002;51:2968-2974.
58 Yang WS, Jeng CY, Wu TJ, et al. Synthetic peroxisome proliferators-activated receptor-gama agonist, rosiglitazone, increases plasma levels of adiponectin in type 2 diabetic patients. Diabetes Care 2002;25:376-380.
59 Neschen S, Morino K, Rossbacher JC, et al. Fish oil regulates adiponectin secretion by a peroxisome proliferators-activated receptor-y-dependent mechanism in mice. Diabetes 2006;55:924-928.
60 Argmann CA, Sawyez CG, McNeil CJ, et al. Activation of peroxisome proliferators-activated receptor gamma and retinoid X receptor results in net depletion of cellular cholesteryl esters in macrophages exposed to oxidized lipoproteins. Arterioscler Thromb Vasc Biol 2003;23:475-482.
61 Chinetti G, Gbaguidi FG, Griglio S, et al. CLS/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferators-activated receptor. Circulation 2000; 101:2411-2417.
62 Ricote M, Li AC, Willson TM, et al. The peroxisome proliferators-activated receptor y is a negative regulator of macrophage activation. Nature 1998;391:79-82.
63 Bodies AM, Varma V, Yao-Borengasser A, et al. Pioglitazone induces apoptosis of macrophages in human adipose tissue. J Lipid Res 2006;47:2080-2088.
1 David R.Recent progress in defining the role of scavenger receptors in lipid transport,atherosclerosis and host defence.Curr opin in Lipid,1998,9:425-432.
2 Febbraio M,Hajjar DP,Silverstein RL.CD36:a class B scavenger receptor involved in angiogenesis,atherosclerosis,inflammation,and lipid metabolism.J Clin Invest,2001,108:785-791.
3 杨向东,李红霞,王抒等.CD36介导氧化型低密度脂蛋白诱导U937细胞泡沫化和凋亡.中国动脉硬化杂志,2000,8:315-318.
4 Nicholson AC,Han J,Febbraio M,et al.Role of CD36,the macrophage class B scavenger receptor,in atherosclerosis.Ann N Y Acad Sci,2001,947(12):224-228.
5 Nagy L,Tontonoz P,Alvarez JG,et al.Oxidized LDL regulates macrophage gene expression through ligiand activation of PPAR-γ.Cell,1998,93(1):229-240.
6 Marx N,Kehrle B,Kohlhammer K,et al.PPAR activators as antiinflammatary mediators in human T lyphocytes:implications for atherosclerosis and translation associated artheriosclerosis.Circres,2002,4,90(6):703-710.
7 Ricote M,Li AC,Willson TM,et al.The peroxisome proliferators activated receptor γ is a negative regulator of macrophage activation.Nature,1998,391(6662):79-82.
8 Febbraio M, Abumrad NA, Hajjar DP, et al. A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem, 1999, 274:19055-19062.
9 Vidya V, Kunjathoor, Maria Febbraio, et al. Scavenger receptor class A-I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J Biol Chem Vol December,2002, 277,51:49982-49988.
10 Nozaki S, Kashiwagi H, Yamashita S, et al.Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36 deficient subjects. J Clin Invest, 1995,96:1859-1865.
11 Nicholson A, Pearce SFA, Silverstein R. Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site. Arterioscler Thromb, 1995,15:269- 275.
12 Boullier A, Gillotte KL, Horkko S, et al. The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moietied of the lipoprotein. J Biol Chem, 2000,275,9163-9169.
13 Chawla A, Barak Y, Nagy L, et al. PPAR-gamma dependent and independent effents on macrophage-geneexpression in lipoid metabolism and inflammation. Nat Med,2001,7:23-24.
14 Griffin E, Re A, Hamel N, et al. A link between diabetes and atherosclerosis: Glucose regulates expression of CD36 at the level of translation. Nat Med,2001,7: 840-846.
15 Nesrin Kartal O zer a, Yesim Negis. Vitamin E inhibits CD36 scavenger receptor expression in hypercholesterolemic rabbits. Atherosclerosis, article in press, 2005.
16 Fuhrman B, Koren L, Volkova N, et al. Atorvastatin therapy in hypercholesterolomic patients suppresses cellular uptake of oxidized-LDL by differentiating monocytes. Atherosclerosis, 2002,164:179-185.
17 Han J, Zhou X, Yokoyama T, et al. Pitavastatin downregulates expression of the macrophage type Bscavenger receptor, CD36. Circulation, 2004, 17:790-796.
18 Han J, Hajjar DP, Tauras JM, et al. Transforming growth factor-β_1(TGF β_1) and TGF β_2 decrease expression of CD36, the type B scavenger, through mitogen activated protein kinase phosphorylation of peroxisome proliferators activated receptor-gamma. J Biol Chem,2000,275:1241-1246.
19 Moore KJ, Rose ED, Fitzgerald ML, et al. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med,2001,7:41-47.
20 Han J, Hajjar DP, Zhou X, et al. Regulation of peroxisome proliferators-activated receptor-gamma-mediated gene expression. A new mechanism of action for high density lipoprotein. J Biol Chem, 277,2002:23582-23586.
21 CalcoD, Gomez-CoronadoD, SuarezY, et al. Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL and VLDL. J Lipid Res, 1998, 39: 777- 787.
22 Moore KJ. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest, 2005,115:2192-2201.
23 Witztum JL. You are tight too. J Clin Invest,2005,l 15:2072-2075.
© 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 |