ARTERIAL WALL AND ATHEROSCLEROSIS

动脉壁和动脉粥样硬化

• 批准号: 6329998
• 负责人: Herbert Marcus Kagan
• 金额: $ 165.8万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-09-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6329998
• 关键词: artery; atherosclerosis; vascular smooth muscle

In response to injury and in certain disease states such as atherosclerosis, normally quiescent medial smooth muscle cells migrate to the intima where they undergo some rounds of proliferation and deposit abundant quantities of matrix components, thus predominantly contributing to vessel occlusion. This Program Project is dedicated to the investigation of molecular mechanisms of regulation of the production of matrix macromolecules by arterial smooth muscle cells in culture and in transgenic mice and vascular tissue models in response to agents and conditions implicated in atherogenesis. We hypothesize that common factors or mechanisms may link the fibrogenic and proliferative capacities of the arterial smooth muscle cells, detailed knowledge of which should elucidate potentially effective means of controlling arterial disease. The first project will principally address the factors affecting B-myb expression and the mechanism by which B-myb down-regulates matrix gene expression. The second project will explore the role of adenosine and its arterial smooth muscle cell receptors in vascular function and matrix protein production. The third project will pursue the analysis of transcriptional and post-transcriptional mechanisms by which smooth muscle cell lysyl oxidase is regulated and will explore the potential function of this amine oxidase within the nucleus of these cells. The fourth project is focused on the regulation of elastin production of IGF-I, addressing the interplay of cis- and trans-acting factors influencing both elastin gene transcription and events related to G1 progression in the cell cycle. The research of these closely integrated projects will rely upon the services of the Biomodel Core which will provide cell culture models and analytical services for analysis of transgenic models. Thus, this Core and the Administrative Core will facilitate a highly interactive approach to achieve the goals set forth. The proposed studies should enhance our understanding of the mechanisms that regulate matrix production and vascular function in normal and pathological conditions.

在受伤和某些疾病状态下，如 动脉粥样硬化，通常静止的中膜平滑肌细胞迁移到 它们经历了几轮增殖和沉积的内膜 大量的基质成分，因此主要贡献 到血管闭塞。本计划项目致力于 黄瓜生产调控的分子机制研究进展 动脉平滑肌细胞在培养和培养过程中产生的基质大分子 转基因小鼠和血管组织模型对药物和 与动脉粥样硬化形成有关的条件。我们假设共同因素 或机制可能联系成纤维形成和增殖的能力 动脉平滑肌细胞，对其详细了解应予以阐明 控制动脉疾病的潜在有效手段。 第一个项目将主要解决影响B-MYB的因素 B-myb下调基质基因表达及其机制的研究 表情。第二个项目将探索腺苷及其受体的作用。 血管功能和基质中的动脉平滑肌细胞受体 蛋白质生产。第三个项目将继续分析 平滑肌细胞的转录和转录后机制 细胞赖氨酰氧化酶受到调控，并将探索其潜在功能 这些细胞胞核内的这种胺氧化酶。第四个项目 重点是调节IGF-I的弹性蛋白生产，解决 影响弹性蛋白的顺式和反式作用因素的相互作用 细胞周期中与G1进程相关的基因转录和事件。 这些紧密结合的项目的研究将依赖于 Biomodel Core的服务，它将提供细胞培养模型和 用于转基因模型分析的分析服务。因此，这个核心和 行政核心将促进以高度互动的方式 实现设定的目标。建议的研究应可加强我们的 了解调节基质产生的机制和 正常和病理状态下的血管功能。