Jilma Bernd, Joukhadar Christian, Derhaschnig Ulla, Rassoul Fausi, Richter Volker, Wolzt Michael, Dorner Guido T, Petternel Vanessa, Wagner Oswald F
Department of Clinical Pharmacology-TARGET, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
Clin Sci (Lond). 2003 Feb;104(2):189-93. doi: 10.1042/CS20020168.
Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4-4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2-4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6-6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n =19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.
对动物和人类的研究表明，黏附分子（AMs）在动脉粥样硬化的发病机制中起关键作用。虽然已有人提出高胆固醇血症与AM表达之间存在关联，但尚不清楚降低胆固醇是否会降低AM的表达和释放。在一项随机临床试验中，我们比较了用三种不同他汀类药物（阿托伐他汀、辛伐他汀和普伐他汀）的标准剂量进行3个月治疗对75例高胆固醇血症患者循环AM（cAM）血浆水平的影响。在治疗3个月前后，测量了循环（c）E-选择素、循环细胞间黏附分子-1（cICAM-1）和循环血管细胞黏附分子-1（cVCAM-1）的血浆水平。没有一种他汀类药物能降低血浆cAM水平，对所有患者的汇总分析显示，cE-选择素增加了1.7%[95%置信区间（CI），-1.4 - 4.9%]，cICAM-1增加了2.1%（95%CI，-0.2 - 4.4%），cVCAM-1水平增加了2.7%（95%CI，-0.6 - 6.1%）。即使在低密度脂蛋白胆固醇水平降低>50%的患者（n = 19）中，cAM水平也没有下降。这项研究提供了强有力的证据，表明在中度高胆固醇血症患者中，尽管胆固醇水平恢复正常且C反应蛋白水平略有下降，但用三种不同他汀类药物进行3个月治疗并不会降低cAM水平。
