权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Structural and functional analysis of phenotypic modulation of vascular smooth muscle cell

血管平滑肌细胞表型调节的结构和功能分析

基本信息

批准号：
07457216
负责人：
SAITO Yasushi
金额：
$ 2.69万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

项目摘要

The purpose of this study is to investigate the mechanisms for the phenotypic modulation of vascular smooth muscle cells, which is implicated in the development of atherosclerosis. The study was initiated by our previous observation that the intimal smooth muscle cells show amplified growth potential as well as migratory activity, and they efficiently incorporate the denatured lipoprotein to become foam cells like macrophages. In the present study, we have found that type IV collagen treatment of endothelial cells suppresses the expression of vascular cell adhesion molecule-1, suggesting that vascular smooth muscle cells can change the phenotype of the endothelial cells by secretion of extracellular matrices and such phenomenon plays some role in the developmental process of atherosclerosis. Next, we found that TGF-beta1 administration enhances intimal thickening of the legions made by ballon catheter injury in rabbits, indicating that TGF-beta produced by various cells in atherosclerotic legions accelerates the progression of atherosclerosis possible by promoting the secretion of extracellular matrices from the vascular smooth muscle cells. Finally, we also found that focal adhesion kinase plays an important role in the intracellular signal transduction for chemotaxis stimulated by platelet-derived growth factor downstream of phosphatidylinositol 3-kinase. The findings will reveal the molecular mechanism of the chemotactic signaling inside the cells in response to various extracellular stimuli.

本研究的目的是探讨血管平滑肌细胞的表型调节机制，这是牵连在动脉粥样硬化的发展。该研究是由我们先前的观察开始的，即内膜平滑肌细胞显示出放大的生长潜力以及迁移活性，并且它们有效地掺入变性脂蛋白，成为像巨噬细胞一样的泡沫细胞。在本研究中，我们发现IV型胶原处理的内皮细胞抑制血管细胞粘附分子-1的表达，这表明血管平滑肌细胞可以通过分泌细胞外基质改变内皮细胞的表型，这种现象在动脉粥样硬化的发展过程中发挥了一定的作用。接下来，我们发现TGF-β 1给药增强了兔球囊导管损伤引起的军团内膜增厚，表明动脉粥样硬化军团中各种细胞产生的TGF-β可能通过促进血管平滑肌细胞分泌细胞外基质来加速动脉粥样硬化的进展。最后，我们还发现黏着斑激酶在磷脂酰肌醇3-激酶下游的血小板衍生生长因子刺激的趋化性的细胞内信号转导中起重要作用。这一发现将揭示细胞内对各种细胞外刺激的趋化信号的分子机制。