Okapcova J, Gabor D
Department of Internal Medicine, Centre of Diabetology, F. D. Roosevelt Hospital, Banska Bystrica, Slovakia.
Angiology. 2004 Nov-Dec;55(6):629-39. doi: 10.1177/00033197040550i604.
Cell adhesion molecules are thought to play a role in atherosclerosis. Several clinical trials have shown that fibrate treatment leads to a reduction in coronary events, although the mechanisms are not fully understood. Soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin plasma concentrations were measured in 10 obese dyslipidemic men (group A), in 10 obese dyslipidemic type 2 diabetic men without coronary artery disease (CAD) (group B), and in 10 dyslipidemic type 2 diabetic men with angiographically documented CAD (group C) before and after 12 weeks of treatment with ciprofibrate. Compared with nondiabetic dyslipidemic men, diabetic patients with CAD or without documented CAD had significantly increased levels of sVCAM-1 (512 +/-39 versus 750 +/-139 ng/mL; p<0.0001 and 566 +/-78 ng/mL; p<0.01, respectively) and sE-selectin (54.8 +/-6.9 versus 65.9 +/-8.8 ng/mL; p<0.001 and 62.6 +/-9.4 ng/mL; p=0.056, respectively). The levels of sICAM-1 were similar in all 3 groups. Multivariate analyses showed that the higher sCAM levels in patients occurred independently of lipoprotein levels. Waist circumference as a marker of abdominal adiposity was the only independent predictor of elevated concentrations of all 3 cell adhesion molecules in multivariate analyses. sE-selectin was associated with HbA1C levels (p<0.01) in diabetic men at baseline. After 12 weeks of ciprofibrate therapy, sVCAM-1 levels were reduced by 13.5 +/-2.1%, sICAM-1 levels by 11.8 +/-2.2%, and sE-selectin levels by 17.1 +/-3.5% (p<0.01 for all) with the greatest sE-selectin reduction in the diabetic subgroups (p<0.001). There was no correlation between the lowering of soluble adhesion molecules and the magnitude of lipid-lowering effect. An increased level of circulating adhesion molecules may be a mechanism by which dyslipidemia and/or diabetes mellitus promotes atherogenesis, and treatment with ciprofibrate may alter vascular cell activation.
细胞黏附分子被认为在动脉粥样硬化中发挥作用。多项临床试验表明，贝特类药物治疗可降低冠心病事件的发生率，尽管其机制尚未完全明确。在10名肥胖血脂异常男性（A组）、10名无冠状动脉疾病（CAD）的肥胖血脂异常2型糖尿病男性（B组）以及10名经血管造影证实患有CAD的血脂异常2型糖尿病男性（C组）中，在环丙贝特治疗12周前后测量了可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性细胞间黏附分子-1（sICAM-1）和可溶性E-选择素的血浆浓度。与非糖尿病血脂异常男性相比，患有CAD或未记录CAD的糖尿病患者的sVCAM-1水平显著升高（分别为512±39对750±139 ng/mL；p<0.0001和566±78 ng/mL；p<0.01）以及sE-选择素水平显著升高（分别为54.8±6.9对65.9±8.8 ng/mL；p<0.001和62.6±9.4 ng/mL；p=0.056）。sICAM-1水平在所有3组中相似。多变量分析显示，患者中较高的sCAM水平独立于脂蛋白水平出现。腰围作为腹部肥胖的标志物是多变量分析中所有3种细胞黏附分子浓度升高的唯一独立预测因素。在基线时，sE-选择素与糖尿病男性的糖化血红蛋白水平相关（p<0.01）。环丙贝特治疗12周后，sVCAM-1水平降低了13.5±2.1%，sICAM-1水平降低了11.8±2.2%，sE-选择素水平降低了17.1±3.5%（所有p<0.01），糖尿病亚组中sE-选择素降低幅度最大（p<0.001）。可溶性黏附分子的降低与降脂效果的大小之间没有相关性。循环黏附分子水平升高可能是血脂异常和/或糖尿病促进动脉粥样硬化形成的一种机制，而环丙贝特治疗可能改变血管细胞的激活状态。
