瑞舒伐他汀对急性冠脉综合征患者炎症因子的影响
|
摘要
目的探讨瑞舒伐他汀对急性冠状动脉综合征病人血清白细胞介素-18(IL-18)、C-反应蛋白(CRP)的影响,从而进一步研究其抗炎机制,从而更好的指导临床,并监测其降脂效果。
方法选取在我院心内科住院并行冠脉造影术证实存在冠脉狭窄的不稳定型心绞痛病人30例,稳定型心绞痛病人20例,以20例健康人作为正常对照组,用酶联免疫吸附法(ELISA)测定其血IL-18,免疫比浊法测定C反应蛋白水平。不稳定型心绞痛和稳定型心绞痛病人入院空腹12小时后采血测定IL-18和CRP水平并记录不稳定型心绞痛患者血清甘油三酯、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。不稳定型心绞痛病人入院采血后每晚给予瑞舒伐他汀10mg,每日1次,共用药6周,记录其治疗后血脂水平,并测定血IL-18和CRP水平。
结果正常健康对照组、稳定型心绞痛组和不稳定型心绞痛组各组间的血清IL-18和CRP水平不同,差别有统计学意义(F=190.961,P＜0.01;F=22.359,P＜0.01),稳定型心绞痛组的血清IL-18和CRP高于正常健康对照组,不稳定型心绞痛组的血清IL-18和CRP高于稳定型心绞痛组。不稳定型心绞痛组给予瑞舒伐他汀治疗后血清胆固醇和低密度脂蛋白胆固醇水平明显下降,高密度脂蛋白胆固醇水平显著升高,差异有统计学意义(P＜0.05),IL-18和CRP水平均明显下降,差异有统计学意义(t=12.553,P＜0.01;t=7.991,P＜0.01)。
结论(1)炎症是冠心病的发病机制之一,参与动脉粥样硬化病变的发生、发展,IL-18和CRP是反映冠脉粥样病变的炎症反应的重要指标,在斑块的不稳定性中发挥重要的作用。(2)瑞舒伐他汀除能降低急性冠状动脉综合征患者的血清胆固醇、低密度脂蛋白胆固醇水平,提高高密度脂蛋白胆固醇水平之外,并能显著降低其炎症反应,稳定斑块。
Objective To study effects of rosuvastatin on plasma intefleukin-18(IL-18) and C-creactive protein(CRP) levels in patients with acute coronary syndrome and to investigate the effects of rosuvastatin on decreasing blood lipid level.
Methods All patients with coronary heart disease were divided into two groups, including 30 cases of unstable angina group,20 cases of stable angina group,there were 20 cases in normal control group,levels of IL-18,CRP were detected.Unstable angina group was given rosuvastatin(10mg a day) every night for 6 weeks.Levels of TG,TC,HDL,LDL,IL- 18,CRP were measured before and after treatment.
Results The serum levels of IL-18 and CRP were distinctively different in the three groups(F=190.961,P＜0.01;F:22.359,P＜0.01).The serum levels of IL-18 and CRP on patients with coronary heart disease were much higher than nomal control',those in unstable angina group higher than in angina group.Levels of IL-18,CRP in unstable angina group were distinctively lower after treatment(t=12.553,P＜0.01;t=7.991, P＜0.01),and so as TC,LDL,and level of HDL advanced.
Conclusion IL-18 and CRP are the indexes for inflammation of atherosclerosis,it plays an important role in plaque stability.Rosuvastatin can decrease levels of serum TC,LDL,IL-18,CRP in patients with acute coronary syndrome and hoist HDL,reduce inflammation,stable plaque.
方法选取在我院心内科住院并行冠脉造影术证实存在冠脉狭窄的不稳定型心绞痛病人30例,稳定型心绞痛病人20例,以20例健康人作为正常对照组,用酶联免疫吸附法(ELISA)测定其血IL-18,免疫比浊法测定C反应蛋白水平。不稳定型心绞痛和稳定型心绞痛病人入院空腹12小时后采血测定IL-18和CRP水平并记录不稳定型心绞痛患者血清甘油三酯、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。不稳定型心绞痛病人入院采血后每晚给予瑞舒伐他汀10mg,每日1次,共用药6周,记录其治疗后血脂水平,并测定血IL-18和CRP水平。
结果正常健康对照组、稳定型心绞痛组和不稳定型心绞痛组各组间的血清IL-18和CRP水平不同,差别有统计学意义(F=190.961,P＜0.01;F=22.359,P＜0.01),稳定型心绞痛组的血清IL-18和CRP高于正常健康对照组,不稳定型心绞痛组的血清IL-18和CRP高于稳定型心绞痛组。不稳定型心绞痛组给予瑞舒伐他汀治疗后血清胆固醇和低密度脂蛋白胆固醇水平明显下降,高密度脂蛋白胆固醇水平显著升高,差异有统计学意义(P＜0.05),IL-18和CRP水平均明显下降,差异有统计学意义(t=12.553,P＜0.01;t=7.991,P＜0.01)。
结论(1)炎症是冠心病的发病机制之一,参与动脉粥样硬化病变的发生、发展,IL-18和CRP是反映冠脉粥样病变的炎症反应的重要指标,在斑块的不稳定性中发挥重要的作用。(2)瑞舒伐他汀除能降低急性冠状动脉综合征患者的血清胆固醇、低密度脂蛋白胆固醇水平,提高高密度脂蛋白胆固醇水平之外,并能显著降低其炎症反应,稳定斑块。
Objective To study effects of rosuvastatin on plasma intefleukin-18(IL-18) and C-creactive protein(CRP) levels in patients with acute coronary syndrome and to investigate the effects of rosuvastatin on decreasing blood lipid level.
Methods All patients with coronary heart disease were divided into two groups, including 30 cases of unstable angina group,20 cases of stable angina group,there were 20 cases in normal control group,levels of IL-18,CRP were detected.Unstable angina group was given rosuvastatin(10mg a day) every night for 6 weeks.Levels of TG,TC,HDL,LDL,IL- 18,CRP were measured before and after treatment.
Results The serum levels of IL-18 and CRP were distinctively different in the three groups(F=190.961,P＜0.01;F:22.359,P＜0.01).The serum levels of IL-18 and CRP on patients with coronary heart disease were much higher than nomal control',those in unstable angina group higher than in angina group.Levels of IL-18,CRP in unstable angina group were distinctively lower after treatment(t=12.553,P＜0.01;t=7.991, P＜0.01),and so as TC,LDL,and level of HDL advanced.
Conclusion IL-18 and CRP are the indexes for inflammation of atherosclerosis,it plays an important role in plaque stability.Rosuvastatin can decrease levels of serum TC,LDL,IL-18,CRP in patients with acute coronary syndrome and hoist HDL,reduce inflammation,stable plaque.
引文
[1]李崇剑,高润霖,杨跃进,等.易损斑块的病理生理机制及其检验的研究[J].中华心血管并杂志,2004,32(6):570-572.
[2]Williama KJ,Tabas i.Atherosclerosis and inflammation.Science,2002,297(5581):521-522.
[3]王红,郑延松.非冠心病患者未来发生心血管疾病可能性预测中高敏C反应蛋白的作用[J].中国临床康复.2004,8(12):2364-2366.
[4]ALBERTMA,DANIELSON E,RIFAI N,et al.Effect of statin therapy on C reactive protein levels;pravastatin inflammation/CRP evaluation(PRINCE):a randomized trial andcohort study[J].JAVA,2001,286(1):64-70.
[5]Yoshimoto T,Takeda K,Tanaka T,et al.IL-12 up-regulates IL-18 receptor expression on T cells,Th1 cells and B cells:synergism with IL-18 for IFN-γ production[J].J Immunol,1998,161(7):3400-3407.
[6]de Nooijer R,vonder Thusen J H,Verkleij CJ,et al.Overexpression of IL-18decreases intimal collagen content and promotes a vulnerable plaque in apolipoprotein-E-deficient mice[J].Arterioscler Thromb Vase Biol,2004,23(12):2313-2319.
[7]Pasceri V,Willerson JT,Yeh ET.Direct proinfammatory effect of C-reactive protein on human endothelial cell[J].Circulation,2000,102(18):2165-2168.
[8]PEASON TA,MENSAH GA,ALEXANDER RW,et al.Markers of inflammation and cardiovascular disease:application to clinical and public health practice:a statement for heal theare professionals from the centers for disease control and prevention and the American Heart Association[J].Circulation,2003,107(3):499-511.
[9]NOVICK D,DINARELLO CA,RUBINSTEIN M.Soluble IL-18 receptor in human urine:characterization and purification(abstract)[J].Cytokine,1997,9:963.
[10]Yamaoko Tojo M,Tojo T,Masuda T,et al.Heart Vessels,2003,18(4):183-187.
[11]MALLAT Z,CORBAZ A,SCOAZEC A,et al.Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability[J].Circulation,2001,04 (14):1598-1603.
[12]Ziad M,Henry P,Fressonnet R,et al.Increased plasma concentrations of interleukin-18 in acute coronary sondromes[J].Haert,2002,88:467.
[13]Yukihiro S,Tsugiyasu K,Toru T,et al.Interleukin-18 in myocardial infarction [J].Heart,2000,84:668.
[14]柴锡庆,苏安英,曾瑞红,等.炎性标志物在动脉粥样硬化过程中的变化及其意义[J].中国全科医学,2002,5(10):792.
[15]Zama AG,Helft G.The role if plaque rupture and thrombosis in coronary disease [J].Atherosclerosis,2000,149(2):251.
[16]Torzewski J,Torzewshi M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the termal complement complex in the intima of early atherosclerotic lesion of human coronary arteries[J].Arterioscler Thromb vase boil,1998,18(9):1386.
[17]Jones PH,Davidson MH,Stein EA,et al.Comparison of the efficacy and safety of rosuvastatin versus atorvastatin,simvastatin,and pravastatin across doses(STELLAR Trial)[J].Am J Cardiol,2003,93(1):152-160.
[18]Nissen SE,Nicholls SJ,Sipahi I,eta].Effect of very high-intensity statin therapy on regression of coronary atherosclerosis.The ASTEROD trial[J].JAMA,2006,295(13):1556-1565.
[19]Link A,Ayadhi T,Nickenig G,et al.Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.[J].EUR.HEART J,2006,27(24):2945-2955.
[20]ENDRES M.Statins:Potential new indications in inflammatory conditions[J].Atheroscler Suppl,2006,7(1):31-35.
[21]Wilson SH,Simari RD,Best PJ,et al.Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering[J].Arteroscler Thromb Vasc Biol,2001,21(1):122-128.
[1]Torzewski J,Torzewski M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.Arterioscler Thromb Vasc Biol,1998,18:1386-1392.
[2]Torzewski J,Torzewski M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.Arterioscler Thromb Vasc Biol,1998,18:1386-1392.
[3]Haverkate F,Thompson SG,Pyke SD,et al.Production of C-reactive protein and risk of coronary events in stable and unstable angina.European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group[J].Lancet,1997,349(9050):462-466.
[4]Mendall MA,Patel P,Ballam L,et al.C reactive protein and its relation to cardiovascular risk factor:a population based cross sectional study[J].BMJ,1996,313(7054):428.
[5]Zama AG,Helft G.The role if plaque rupture and thrombosis in coronary disease [J].Atherosclerosis,2000,149(2):251.
[6]Torzewski J,Torzewshi M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the termal complement complex in the intima of early atherosclerotic lesion of human coronary arteries[J].Arterioscler Thromb vase boil,1998,18(9):1386.
[7]Retterstol L,Eikvar L,Bohn M,et al.Is C-reactive protein predicts death in patients with previous premature myocardial infarction-a 10 year follow-up study [J].Atherosclerosis,2002,160(2):433-440.
[8]Okamura H,Tsutsi H,Komatsu T,et al.Nature,1995,378(6552):88-91.
[9]Yamaoka Tojo M,Tojo T,Masuda T,et al.Heart Vessels,2003,18(4):183-187.
[10]Mallat Z,Corbaz A,Scoazec A,et al.Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.Circulation 2001;104(14):1598-60.
[11]Gerdes U,Sukhova GK,Libby P,et al.J Exp Med,2002,195(2):245-257.
[12]Blankenberg S,Luc G,Ducimetiere P,et al.Interleukin-18 and the risk of coronary heart disease in European men:the prospective epidemiological study of myocardial infarction(PRIME)[J].Circulation,2003,108(20):2453-2459.
[13]陈绍良.急性冠状动脉综合征:理论与实践前沿[M].辽宁:辽宁科学技术出版社,2005: 49-51.
[14] Yamashita H, Shimada K,Seki E, et al.Biochem Biophys Res Commun, 2004, 325(4):1187-1193.
[15] Blankenberg S,Tiret L, Bickel C,et al. Circulation, 2002,106(1):24-30.
[16] Blankenberg S,Luc G, Ducimetiere P,et al. Circulation,2003,108(20):2453-2459.
[17] Chandrasekar B, Mummidi S, Mahimainathan L, et al. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-κB-and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin [J]. J Biol Chem,2006, 281 (22): 15099-15109.
[18] Chandrasekar B, Mummidi S, Valente AJ, et al. The proatherogenic cytokine interleukin-18 induces CXCL 16 expression in rat aortic muscle cells via MyD88,interleukin-1 receptor-associated kinase, tumor necrosis factor-associated factor 6,c-Src, phosphatidylinositol 3-kinase, Akt, c-Jun N-terminal kinase, and activator-1 signaling [J]. J Biol Chem, 2005, 280 (28):26263-26277.
[19] Kawasaki D, Tsujino T, Merimoto S, et al. Usefulness of circulating interleukin-18 concentration in acute myocardial imarction as a risk factor for late restenosis after emergency coronary angioplasty [J]. Am J Cardiol, 2003, 91 (10): 1258-1261.
[20] Wassmann S,Paul A, Hennen B, et al. Rapid effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition on coronary endothelial function. Circ Res, 2003, 93(9):98-103.
[21] Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus ezetimibe:pleiotropic and lipid-lowing effects on endothelial function in humans. Circulation, 2005, 111(18):2356-2363.
[22] Nickenig G, Harrison DG. The AT(l)-type angiotensin receptor in oxidative stress and atherogenesis Part I Oxidative stress and atherogenesis [J]. Circulation, 2002, 105:393-396.
[23] Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor[J]. Nature, 1986, 320: 454-456.
[24] Darley-U smar VM, Hogg N, O' Leary VJ, et al. The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein[J]. Free Radic Res Commun, 1992, 17: 920.
[25] Chin JH,Azhar S,Hoffman BB. Inactivation of endothelial-derived relaxing factor by oxidized lipoproteins[J]. J Clin Invest, 1992, 89:10-18.
[26]Rikitaka Y,Kawashima S,Takeshota S,et al.Anti-oxidative properties of fluvastatin,an HMG-CoA reductase inhibitor,contribute to prevention of atherosclerosis in cholesterol-fed rabbits[J].Atherosclerosis,2001,154:87-96.
[27]Rosenson RS,Tangney CC,Casey LC.Inhibition of proinflammatory cytokine production by pravastatin.Lancet,1999,353(9157):983-984.
[28]Ridker PM,Rifai N,Pfeffer MA,et al.Long-term effects of pravastatin on plasma concentration of C-reactive protein[J].Circulation,1999,100:230-235.
[29]Nissen SE,Tuzcu EM,Schoenhagen P,et al.Statin therapy,LDL cholesterol,C-reactive protein,and coronary artery disease[J].N Engl J Med,2005,352:29-38.
[30]王平,楚建民,宋执敬.辛伐他汀读兆时亿年个厘时秒年个 血脂水平急性冠状动脉综合征患者早期炎症因子的干预观察.中国分子心脏病学杂志,2006,6(2):78-80.
[31]Link A,Ayadhi T,Nickenig G,et al.Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.[J].EUR.HEART J,2006,27(24):2945-2955.
[32]Negre Aminou P,van Vliet AK,van Erck M,et al.Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibiters;comparison with other human cell types.Biochim Biophs Acta,1997,1345(3):259-268.
[33]Erl W.Statin-induced vascular smooth muscle cell apoptosis:a possible role in the prevention of restenosis? Curr Drug Targets Cardiovasc Haematol Disord,2005,5(2):135-144.
[34]Fenton JW 2nd,Brezniak DV,Ofosu FA,et al.Statin and thrombin.Curr Drug Targets Cardiovasc Haematol Disord,2005,5(2):115-120.Disord,2005,5(2):135-268.
[35]Schafer K,Kaiser K,Konstantunides s.Rosuvastatin exerts favourable effects on thrombosis and neointimal growth in a mouse model of endothelial injury.Thromb Haemost,2005,93(1):145-152.
[36]Kitamoto S,Nakano K,Hirouchi Y,et al.Cholesterol-lowing independent regression and by stabilization of atherosclerotic lesions by pravastatin and by antimonocyte chemoattractant protein-1 therapy in nonhuman primates.Arterioscle Thromb Vasc Biol,2004,24(8):1522-1528.
[37]Giurgea AG,Margeta C,Maca T,et al.Simvastatin reduces serum level of vascular endothelial growth factor in hypercholesterolemic patients[J].Cardiovasc Pharmacol,2006,47(1):30-36.
[38]Rouleau J.Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimemresults from the Pravastatin or Atorvastatin Evaluation an Infection therapy-Thrombolysis in Myocardial Infarction 22(PROVE IT-TIMI 22) trial. Am J Med 2005 Dec;118 Suppl 12A:28-35.
[39] Heart Protection Study Collaborate Group.MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals:a randomized place-bo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22.
[2]Williama KJ,Tabas i.Atherosclerosis and inflammation.Science,2002,297(5581):521-522.
[3]王红,郑延松.非冠心病患者未来发生心血管疾病可能性预测中高敏C反应蛋白的作用[J].中国临床康复.2004,8(12):2364-2366.
[4]ALBERTMA,DANIELSON E,RIFAI N,et al.Effect of statin therapy on C reactive protein levels;pravastatin inflammation/CRP evaluation(PRINCE):a randomized trial andcohort study[J].JAVA,2001,286(1):64-70.
[5]Yoshimoto T,Takeda K,Tanaka T,et al.IL-12 up-regulates IL-18 receptor expression on T cells,Th1 cells and B cells:synergism with IL-18 for IFN-γ production[J].J Immunol,1998,161(7):3400-3407.
[6]de Nooijer R,vonder Thusen J H,Verkleij CJ,et al.Overexpression of IL-18decreases intimal collagen content and promotes a vulnerable plaque in apolipoprotein-E-deficient mice[J].Arterioscler Thromb Vase Biol,2004,23(12):2313-2319.
[7]Pasceri V,Willerson JT,Yeh ET.Direct proinfammatory effect of C-reactive protein on human endothelial cell[J].Circulation,2000,102(18):2165-2168.
[8]PEASON TA,MENSAH GA,ALEXANDER RW,et al.Markers of inflammation and cardiovascular disease:application to clinical and public health practice:a statement for heal theare professionals from the centers for disease control and prevention and the American Heart Association[J].Circulation,2003,107(3):499-511.
[9]NOVICK D,DINARELLO CA,RUBINSTEIN M.Soluble IL-18 receptor in human urine:characterization and purification(abstract)[J].Cytokine,1997,9:963.
[10]Yamaoko Tojo M,Tojo T,Masuda T,et al.Heart Vessels,2003,18(4):183-187.
[11]MALLAT Z,CORBAZ A,SCOAZEC A,et al.Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability[J].Circulation,2001,04 (14):1598-1603.
[12]Ziad M,Henry P,Fressonnet R,et al.Increased plasma concentrations of interleukin-18 in acute coronary sondromes[J].Haert,2002,88:467.
[13]Yukihiro S,Tsugiyasu K,Toru T,et al.Interleukin-18 in myocardial infarction [J].Heart,2000,84:668.
[14]柴锡庆,苏安英,曾瑞红,等.炎性标志物在动脉粥样硬化过程中的变化及其意义[J].中国全科医学,2002,5(10):792.
[15]Zama AG,Helft G.The role if plaque rupture and thrombosis in coronary disease [J].Atherosclerosis,2000,149(2):251.
[16]Torzewski J,Torzewshi M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the termal complement complex in the intima of early atherosclerotic lesion of human coronary arteries[J].Arterioscler Thromb vase boil,1998,18(9):1386.
[17]Jones PH,Davidson MH,Stein EA,et al.Comparison of the efficacy and safety of rosuvastatin versus atorvastatin,simvastatin,and pravastatin across doses(STELLAR Trial)[J].Am J Cardiol,2003,93(1):152-160.
[18]Nissen SE,Nicholls SJ,Sipahi I,eta].Effect of very high-intensity statin therapy on regression of coronary atherosclerosis.The ASTEROD trial[J].JAMA,2006,295(13):1556-1565.
[19]Link A,Ayadhi T,Nickenig G,et al.Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.[J].EUR.HEART J,2006,27(24):2945-2955.
[20]ENDRES M.Statins:Potential new indications in inflammatory conditions[J].Atheroscler Suppl,2006,7(1):31-35.
[21]Wilson SH,Simari RD,Best PJ,et al.Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering[J].Arteroscler Thromb Vasc Biol,2001,21(1):122-128.
[1]Torzewski J,Torzewski M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.Arterioscler Thromb Vasc Biol,1998,18:1386-1392.
[2]Torzewski J,Torzewski M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.Arterioscler Thromb Vasc Biol,1998,18:1386-1392.
[3]Haverkate F,Thompson SG,Pyke SD,et al.Production of C-reactive protein and risk of coronary events in stable and unstable angina.European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group[J].Lancet,1997,349(9050):462-466.
[4]Mendall MA,Patel P,Ballam L,et al.C reactive protein and its relation to cardiovascular risk factor:a population based cross sectional study[J].BMJ,1996,313(7054):428.
[5]Zama AG,Helft G.The role if plaque rupture and thrombosis in coronary disease [J].Atherosclerosis,2000,149(2):251.
[6]Torzewski J,Torzewshi M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the termal complement complex in the intima of early atherosclerotic lesion of human coronary arteries[J].Arterioscler Thromb vase boil,1998,18(9):1386.
[7]Retterstol L,Eikvar L,Bohn M,et al.Is C-reactive protein predicts death in patients with previous premature myocardial infarction-a 10 year follow-up study [J].Atherosclerosis,2002,160(2):433-440.
[8]Okamura H,Tsutsi H,Komatsu T,et al.Nature,1995,378(6552):88-91.
[9]Yamaoka Tojo M,Tojo T,Masuda T,et al.Heart Vessels,2003,18(4):183-187.
[10]Mallat Z,Corbaz A,Scoazec A,et al.Expression of interleukin-18 in human atherosclerotic plaques and relation to plaque instability.Circulation 2001;104(14):1598-60.
[11]Gerdes U,Sukhova GK,Libby P,et al.J Exp Med,2002,195(2):245-257.
[12]Blankenberg S,Luc G,Ducimetiere P,et al.Interleukin-18 and the risk of coronary heart disease in European men:the prospective epidemiological study of myocardial infarction(PRIME)[J].Circulation,2003,108(20):2453-2459.
[13]陈绍良.急性冠状动脉综合征:理论与实践前沿[M].辽宁:辽宁科学技术出版社,2005: 49-51.
[14] Yamashita H, Shimada K,Seki E, et al.Biochem Biophys Res Commun, 2004, 325(4):1187-1193.
[15] Blankenberg S,Tiret L, Bickel C,et al. Circulation, 2002,106(1):24-30.
[16] Blankenberg S,Luc G, Ducimetiere P,et al. Circulation,2003,108(20):2453-2459.
[17] Chandrasekar B, Mummidi S, Mahimainathan L, et al. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-κB-and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin [J]. J Biol Chem,2006, 281 (22): 15099-15109.
[18] Chandrasekar B, Mummidi S, Valente AJ, et al. The proatherogenic cytokine interleukin-18 induces CXCL 16 expression in rat aortic muscle cells via MyD88,interleukin-1 receptor-associated kinase, tumor necrosis factor-associated factor 6,c-Src, phosphatidylinositol 3-kinase, Akt, c-Jun N-terminal kinase, and activator-1 signaling [J]. J Biol Chem, 2005, 280 (28):26263-26277.
[19] Kawasaki D, Tsujino T, Merimoto S, et al. Usefulness of circulating interleukin-18 concentration in acute myocardial imarction as a risk factor for late restenosis after emergency coronary angioplasty [J]. Am J Cardiol, 2003, 91 (10): 1258-1261.
[20] Wassmann S,Paul A, Hennen B, et al. Rapid effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition on coronary endothelial function. Circ Res, 2003, 93(9):98-103.
[21] Landmesser U, Bahlmann F, Mueller M, et al. Simvastatin versus ezetimibe:pleiotropic and lipid-lowing effects on endothelial function in humans. Circulation, 2005, 111(18):2356-2363.
[22] Nickenig G, Harrison DG. The AT(l)-type angiotensin receptor in oxidative stress and atherogenesis Part I Oxidative stress and atherogenesis [J]. Circulation, 2002, 105:393-396.
[23] Gryglewski RJ, Palmer RM, Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor[J]. Nature, 1986, 320: 454-456.
[24] Darley-U smar VM, Hogg N, O' Leary VJ, et al. The simultaneous generation of superoxide and nitric oxide can initiate lipid peroxidation in human low density lipoprotein[J]. Free Radic Res Commun, 1992, 17: 920.
[25] Chin JH,Azhar S,Hoffman BB. Inactivation of endothelial-derived relaxing factor by oxidized lipoproteins[J]. J Clin Invest, 1992, 89:10-18.
[26]Rikitaka Y,Kawashima S,Takeshota S,et al.Anti-oxidative properties of fluvastatin,an HMG-CoA reductase inhibitor,contribute to prevention of atherosclerosis in cholesterol-fed rabbits[J].Atherosclerosis,2001,154:87-96.
[27]Rosenson RS,Tangney CC,Casey LC.Inhibition of proinflammatory cytokine production by pravastatin.Lancet,1999,353(9157):983-984.
[28]Ridker PM,Rifai N,Pfeffer MA,et al.Long-term effects of pravastatin on plasma concentration of C-reactive protein[J].Circulation,1999,100:230-235.
[29]Nissen SE,Tuzcu EM,Schoenhagen P,et al.Statin therapy,LDL cholesterol,C-reactive protein,and coronary artery disease[J].N Engl J Med,2005,352:29-38.
[30]王平,楚建民,宋执敬.辛伐他汀读兆时亿年个厘时秒年个 血脂水平急性冠状动脉综合征患者早期炎症因子的干预观察.中国分子心脏病学杂志,2006,6(2):78-80.
[31]Link A,Ayadhi T,Nickenig G,et al.Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome.[J].EUR.HEART J,2006,27(24):2945-2955.
[32]Negre Aminou P,van Vliet AK,van Erck M,et al.Inhibition of proliferation of human smooth muscle cells by various HMG-CoA reductase inhibiters;comparison with other human cell types.Biochim Biophs Acta,1997,1345(3):259-268.
[33]Erl W.Statin-induced vascular smooth muscle cell apoptosis:a possible role in the prevention of restenosis? Curr Drug Targets Cardiovasc Haematol Disord,2005,5(2):135-144.
[34]Fenton JW 2nd,Brezniak DV,Ofosu FA,et al.Statin and thrombin.Curr Drug Targets Cardiovasc Haematol Disord,2005,5(2):115-120.Disord,2005,5(2):135-268.
[35]Schafer K,Kaiser K,Konstantunides s.Rosuvastatin exerts favourable effects on thrombosis and neointimal growth in a mouse model of endothelial injury.Thromb Haemost,2005,93(1):145-152.
[36]Kitamoto S,Nakano K,Hirouchi Y,et al.Cholesterol-lowing independent regression and by stabilization of atherosclerotic lesions by pravastatin and by antimonocyte chemoattractant protein-1 therapy in nonhuman primates.Arterioscle Thromb Vasc Biol,2004,24(8):1522-1528.
[37]Giurgea AG,Margeta C,Maca T,et al.Simvastatin reduces serum level of vascular endothelial growth factor in hypercholesterolemic patients[J].Cardiovasc Pharmacol,2006,47(1):30-36.
[38]Rouleau J.Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimemresults from the Pravastatin or Atorvastatin Evaluation an Infection therapy-Thrombolysis in Myocardial Infarction 22(PROVE IT-TIMI 22) trial. Am J Med 2005 Dec;118 Suppl 12A:28-35.
[39] Heart Protection Study Collaborate Group.MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals:a randomized place-bo-controlled trial. Lancet 2002 Jul 6;360(9326):7-22.