GLUCOCORTICOIDS, MACROPHAGES AND THE VULNERABLE PLAQUE

描述：（改编自申请人的摘要）脆弱的斑块是 容易破裂并可能导致急性冠状动脉综合征。 的目标 这些合作项目旨在确定与以下方面有关的机制： 脆弱斑块的形成和稳定， 非侵入性方法进行检测和表征。这 项目的重点是在斑块的巨噬细胞的核心作用 形成和去稳定化。目标1将研究 地塞米松（Dex）影响斑块进展/消退， 单核细胞趋化蛋白-1（MCP-1）的表达， 巨噬细胞的致动脉粥样硬化产物）在诱导的突变小鼠模型中 通过饮食或血管损伤治疗。目标2将侧重于分子 Dex诱导的MCP-1 mRNA不稳定性的调节。在aim 3中，一部小说 将开发和研究小鼠模型，其中巨噬细胞可以 在选定的时间点进行特异性消融，以确定其 在斑块进展、消退以及更重要的破裂中的重要性。 总的来说，这三个项目代表了高度互动的努力， 经验丰富的研究人员将开发新的方法， 易损斑块分子生物学，动物模型，临床 检查和MRI。

DESCRIPTION: (Adapted from Applicant's Abstract) Vulnerable plaques are prone to rupture and can cause acute coronary syndromes. The goal of these collaborative projects are to identify the mechanisms related to the formation and stabilization of vulnerable plaques and to develop non-invasive methods for their detection and characterization. This projects focuses on the central role of the macrophage in plaque formation and de-stabilization. Aim 1 will examine the potential of dexamethasone (Dex) to affect plaque progression/regression and the expression of monocyte chemoattractant protein-1 (MCP-1; a pro- atherogenic product of macrophages) in induced mutant mouse models treated by diet or vessel injury. Aim 2 will focus on the molecular regulation of Dex-induced instability of MCP-1 mRNA. In aim 3, a novel mouse model will be developed and studied in which macrophages can be specifically ablated at selected time points to determine their importance in plaque progression, regression, and importantly, rupture. Overall, the 3 projects represent highly interactive efforts of experienced investigators who will develop new approaches to the vulnerable plaque using molecular biology, animal models, clinical investigation and MRI.