Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow
Simvastatin alters human endothelial cell adhesion molecule expression and inhibits leukocyte adhesion under flow
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DOI：
10.1016/j.atherosclerosis.2007.12.018
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发表时间：
2008-09-01
期刊：
影响因子：
5.3
通讯作者：
Graham, Anne M.
中科院分区：
文献类型：
--
作者：
Eccles, Kirstie A.;Sowden, Heather;Graham, Anne M.
高胆固醇血症是动脉粥样硬化发病机制中的独立危险因素。HMG-CoA还原酶抑制剂（他汀类药物）因其降脂作用而被处方，但最近的证据表明，它们具有不依赖于脂质平衡调节的多效性作用，这可能解释了它们在显著降低心血管死亡率和发病率方面的作用。其机制尚不清楚，但内皮细胞（EC）功能障碍是关键。为了研究他汀类药物对EC的潜在抗炎特性，研究了生理流动条件下人脐静脉内皮细胞（HUVEC）和人中性粒细胞的功能反应。组胺刺激导致中性粒细胞和EC之间的瞬时相互作用显著增加（p < 0.001）。这些作用在用他汀类药物预处理后显著降低（p < 0.001）。TNF-α刺激导致滚动相互作用显著增加（p < 0.001）。在用他汀类药物预处理EC后，这些作用显著降低（p < 0.001）。EC的甲羟戊酸预处理显著逆转了他汀预处理对栓系和滚动的影响（p < 0.001）。暴露于组胺的EC显示P-选择素水平显著增加（p < 0.01），用他汀预处理可消除（p < 0.001）。暴露于TNF-α的EC显示E-选择素水平显著增加（p < 0.001），用他汀预处理降低（p < 0.05）。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Hypercholesterolaemia is implicated as an independent risk factor in the pathogenesis of atherosclerosis. HMG-CoA reductase inhibitors (statins) are prescribed for their lipid-lowering effects but recent evidence suggests they have pleiotropic effects independent of lipid balance regulation that may explain their role in dramatically decreasing cardiovascular mortality and morbidity. The mechanisms responsible are unclear but endothelial cell (EC) dysfunction is critical. To investigate potential anti-inflammatory properties of statins on EC, functional responses of human umbilical vein endothelial cells (HUVEC) and human neutrophils under physiological flow conditions were studied. These interactions were quantified in response to inflammatory mediators following pre-treatment with statin.Histamine stimulation resulted in significant (p < 0.001) increases in transient interactions between neutrophils and EC (tethering). These effects were significantly reduced (p < 0.001) on pre-treatment with statin. TNF-alpha stimulation resulted in significant (p < 0.001) increases in rolling interactions. These effects were significantly (p < 0.001) reduced following pre-treatment of EC with statin. Mevalonate pre-treatment of EC significantly reversed the effects of statin pre-treatment on both tethering and rolling (p < 0.001).Reductions in surface expression of P- and E-selectin were confirmed by ELISA. EC exposed to histamine demonstrated significantly increased (p < 0.01) levels of P-selectin, abrogated (p < 0.001) by pre-treatment with statin. EC exposed to TNF-alpha demonstrated a significant increase (p < 0.001) in levels of E-selectin, reduced (p < 0.05) by pre-treatment with statin. (C) 2008 Elsevier Ireland Ltd. All rights reserved.