期刊
ATHEROSCLEROSIS
卷 148, 期 1, 页码 75-85出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0021-9150(99)00241-5
关键词
platelets; endothelium; monocyte chemotactic protein-1; intercellular adhesion molecule-1; nuclear factor-kappa B; atherogenesis
Platelets and alterations of chemotactic and adhesive properties of endothelium play an important role in the pathophysiology of atherosclerosis. We investigated the effect of platelets on secretion of monocyte chemotactic protein-1 (MCP-I) and on surface expression of intercellular adhesion molecule-1 (ICAM-1) of cultured endothelium. Pretreatment of cultured monolayers of endothelial cells with alpha-thrombin-activated platelets significantly enhanced secretion of MCP-1 and ICAM-1 surface expression (P < 0.01) that could be inhibited by interleukin-l (IL-I) antagonists by approximately 40%. Activation of transcription factor nuclear factor-kappa B (NF-kappa B) which regulates transcription of early inflammatory response genes such as MCP-1, was significantly increased in endothelial cells treated with activated platelets via an IL-I mediated mechanism as determined by electrophoretic mobility shift assay (EMSA) and kappa B-dependent transcriptional activity. In trans-well experiments, alpha-thrombin-activated platelets enhanced IL-1-dependent surface expression of vitronectin receptor (alpha(v)beta(3)) on the luminal aspect of endothelial monolayers and promoted alpha(v)beta(3)-mediated platelet/endothelium adhesion that could be inhibited by the antiadhesive peptides GRGDSP and c(RGDfV). We conclude that activated platelets induce significant changes in chemotactic (secretion of MCP-I) and adhesive (surface expression of ICAM-1 and alpha(v)beta(3)) properties of cultured endothelium. These findings imply a potential pathophysiological mechanism of platelets in an early stage of atherogenesis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据