Ezetimibe inhibits platelet activation and uPAR expression on endothelial cells

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• 作者：Tobias Becher^a ; ¹ ; Torsten J Schulze^b ; ¹ ; Melanie Schmitt^a ; Frederik Trinkmann^a ; Ibrahim El-Battrawy^a ; Ibrahim Akin^a ; Thorsten Kä ; lsch^c ; Martin Borggrefe^a ; Ksenija Stach^a ; ^{ks.stach@gmx.de}
• 关键词：Platelets ; Endothelial cells ; Ezetimibe ; Inflammation ; Atherosclerosis
• 刊名：International Journal of Cardiology
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：227
• 期：Complete
• 页码：858-862
• 全文大小：390 K
• 卷排序：227

文摘

Lipid lowering therapy constitutes the basis of cardiovascular disease therapy. The purpose of this study was to investigate effects of ezetimibe, a selective inhibitor of intestinal cholesterol absorption, on platelets and endothelial cells in an in vitro endothelial cell model.MethodsAfter a 24 h incubation period with ezetimibe (concentrations 1, 50, 100 and 1000 ng/ml), human umbilical vein endothelial cells (HUVEC) were stimulated for 1 h with lipopolysaccharide (LPS) and were then incubated in direct contact with activated platelets. Following this, the expression of CD40L and CD62P on platelets, and the expression of ICAM-1, VCAM-1, uPAR, and MT1-MMP on endothelial cells were measured by flow cytometry. Supernatants were analysed by enzyme linked immunosorbent assay for soluble MCP-1, IL-6 and MMP-1.ResultsThe increased expression of uPAR on endothelial cells by proinflammatory stimulation with LPS and by direct endothelial contact with activated platelets was significantly reduced through pre-incubation with 100 ng/ml and 1000 ng/ml ezetimibe (p < 0.05). Platelets directly incubated with ezetimibe but without endothelial cell contact showed significantly reduced CD62P and CD40L surface expression (p < 0.05). Ezetimibe had no significant effects on HUVEC expression of MT1-MMP, ICAM-1 and VCAM-1 and on CD40L expression on platelets in direct contact with endothelial cells. Levels of soluble IL-6 in HUVEC supernatants were significantly lower after pre-incubation with ezetimibe.ConclusionIn this in vitro analysis, ezetimibe directly attenuates platelet activation and has significant endothelial cell mediated effects on selected markers of atherosclerosis.