EFFECT OF MECHANICAL FORCES ON AGING VASCULAR CELLS

本项目将研究血管的体外细胞衰老。 机械力作用下的内皮细胞及其功能 对基质合成的影响。我们进行这些研究的理由如下：(1) 由于动脉粥样硬化是一种涉及结缔组织的主要疾病 在老年人中发病率明显更高的变化，以及 由于受影响的主要细胞类型是内皮细胞和平滑肌细胞 细胞，宜确定基质合成之间的关系 和衰老，(2)动脉粥样硬化的变化发生在很长一段时间内(年) 我们的系统将允许我们在体外模拟这一时间框架，以及(3) 机械刺激影响细胞新陈代谢的机制 蛋白质的合成还有待于阐明。在本研究中，我们 计划利用血管细胞来检查其他几个专门的 内皮细胞的功能。我们将调查合成的速度 基质蛋白，如胶原蛋白和纤维连接蛋白。此外，我们还将 自始至终调查机械力对这些比率的影响 它们的复制寿命。我们还将确定是否应用 机械力改变了这些细胞的体外寿命。 我们还将确定矩阵分量是否在 用免疫组织化学方法对细胞进行机械拉伸或应激处理。 将进行光学和电子显微镜研究，以评估 这些变化。

This project will investigate the in vitro cellular senescence of vascular endothelial cells which have been subjected to mechanical forces and its effects on matrix synthesis. Our rationale for these studies is: (1) since atherosclerosis is a major disease involving connective tissue changes whose incidence is significantly higher in older individuals, and since the major cell types affected are endothelial and smooth muscle cells, it is appropriate to determine the relation between matrix synthesis and aging, (2) atherosclerotic changes occur over a long time frame (years) and our system will permit us to model this time frame in vitro, and (3) the mechanism by which mechanical stimulation may affect cell metabolism and protein synthesis remains to be elucidated. In the present study, we plan to utilize vascular cells to examine several other specialized functions of endothelium. We will investigate the rate of synthesis of matrix proteins such as collagen and fibronectin. In addition, we will investigate the effects of mechanical forces on these rates throughout their replicative life-span. We will also determine if application of mechanical forces alters the in vitro life-span of these cells. We will also determine if a redistribution of matrix components occurs in mechanically strained or stressed cells by using immunohistochemistry. Light and electron microscopic studies will be carried out to evaluate these changes.