GENOMIC AND GENETIC APPROACHES TO PLAQUE RUPTURE

斑块破裂的基因组学和遗传学方法

• 批准号: 6668562
• 负责人: Stephen MARK Schwartz
• 金额: $ 241.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668562
• 关键词: atherosclerosis; atherosclerotic plaque; clinical research; gene expression; genetic polymorphism; genome

DESCRIPTION (provided by applicant): Despite all the advances in atherosclerosis over the last several decades, surprisingly we lack direct evidence of the critical factors controlling the final events that convert an atherosclerotic lesion from a collection of fatty foam cells to an occlusive, ruptured, procoagulant, and life threatening lesion. The bulk of the evidence supports the hypothesis that these final events occur as a result of inflammatory changes in the lesion. This program projects attempts to test that hypothesis by combining newly developed approaches that allow us to directly visualize the plaque non-invasively in humans with experimental models in the mouse. The human studies will utilize state of the art genomics, including single nucleotide polymorphisms and expression arrays to determine the correlation of specific inflammatory genes with plaque progression. The animal studies will utilize a mouse model of plaque rupture to examine the role of the same genes as manifest in the plaque macrophage and the endothelial cell in these final critical events.

描述（由申请人提供）： 尽管在过去几十年中动脉粥样硬化的所有进展，令人惊讶的是，我们缺乏控制最终事件的关键因素的直接证据，这些事件将动脉粥样硬化病变从脂肪泡沫细胞的集合转化为闭塞性、破裂、促凝和危及生命的病变。 大部分证据支持这一假设，即这些最终事件的发生是由于病变的炎症变化。 该项目试图通过结合新开发的方法来测试这一假设，这些方法使我们能够直接在人类中非侵入性地观察斑块，并在小鼠中建立实验模型。 人类研究将利用最先进的基因组学，包括单核苷酸多态性和表达阵列，以确定特定炎症基因与斑块进展的相关性。 动物研究将利用斑块破裂的小鼠模型来检查与斑块巨噬细胞和内皮细胞中表现的相同基因在这些最终关键事件中的作用。