Vascular Cell Death and Proliferation: Role of Mechanical Stretch

9908591 Liu旁路静脉移植物通常用于替换心脏、大脑和其他器官中阻塞的动脉。不幸的是，由于动脉粥样硬化，静脉移植物通常在数月至数年内失效。尽管进行了广泛的研究，但静脉移植物动脉粥样硬化在如此短的时间内发生的原因仍不清楚。最近的研究表明，由于动脉血压，静脉移植物暴露于拉伸力。这种力与早期血管细胞死亡有关，随后是大量血管细胞生长，这有助于静脉移植物动脉粥样硬化。本研究旨在通过培养的静脉移植物模型来研究这些事件的相关机制。为了阐明拉伸力如何诱导血管细胞死亡和生长，将在细胞培养箱中使用脉动心脏泵模拟静脉移植物，用培养液灌注大鼠颈静脉到不同的压力水平。拉伸力和细胞死亡率之间的关系，以及拉伸力和细胞生长率之间的关系，将使用生物力学方法确定;和生化因素在拉伸诱导的细胞死亡和生长的调解中的作用将使用生物学方法进行检查。拉伸力对细胞死亡和生长的影响将与其他因素（如手术创伤和血流改变）的影响区分开来。此外，还将关注血管细胞死亡和生长之间的关系，并对这些实验数据进行分析，回答以下问题：拉伸力是否在血管细胞死亡和生长中发挥作用;细胞死亡与细胞生长之间的关系;以及可能涉及的机制。本研究将为静脉移植物动脉粥样硬化和失败的机制提供基础信息。

9908591LiuBypass vein grafts are commonly used to replace blocked arteries in the heart, brain, and other organs. Unfortunately, vein grafts often fail within months to years due to atherosclerosis. In spite of extensive investigations, it remains unclear why vein graft atherosclerosis occurs within such a short period. Recent research has demonstrated that a vein graft is exposed to a stretching force due to arterial blood pressure. This force is associated with early vascular cell death, followed by massive vascular cell growth, which contribute to vein graft atherosclerosis. This project is designed to investigate the mechanisms related to these events by using a cultured vein graft model.To clarify how a stretching force induces vascular cell death and growth, rat jugular veins will be perfused with culture media to various pressure levels using a pulsatile cardiac pump to simulate vein grafts in a cell incubator. A relationship between the stretching force and the rate of cell death, as well as between the stretching force and the rate of cell growth, will be determined using a biomechanical approach; and the role of biochemical factors in the mediation of stretch-induced cell death and growth will be examined using biological approaches. The influence of the stretching force on cell death and growth will be distinguished from that of other factors, such as surgical trauma and altered blood flow. Attention will be also given to the relationship between vascular cell death and growth.Data from these experiments will be analyzed and used to answer these questions: whether a stretching force plays a role in vascular cell death and growth; how cell death is related to cell growth; and what mechanisms are possibly involved. This project will provide fundamental information into the mechanisms of vein graft atherosclerosis and failure.