GENOMIC AND GENETIC APPROACHES TO PLAQUE RUPTURE

描述(由申请人提供)： 尽管动脉粥样硬化在过去几十年中取得了所有进展，但令人惊讶的是，我们缺乏控制最终事件的关键因素的直接证据，这些因素将动脉粥样硬化病变从一组脂肪泡沫细胞转变为闭塞、破裂、促凝剂和危及生命的病变。大多数证据支持这一假设，即这些最终事件是由于病变中的炎性变化而发生的。这个项目试图通过结合新开发的方法来验证这一假设，这些方法允许我们在人类身上直接以非侵入性的方式显示斑块，并在老鼠身上建立实验模型。人类研究将利用最先进的基因组学，包括单核苷酸多态和表达阵列来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斑块巨噬细胞和内皮细胞中相同的基因在这些最终关键事件中的作用。

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.