GLUCOCORTICOIDS, MACROPHAGES AND THE VULNERABLE PLAQUE

描述：(改编自申请者摘要)易损斑块 容易破裂，并可能导致急性冠脉综合征。的目标是 这些协作项目是为了确定与以下方面相关的机制 易损斑块的形成、稳定及发展 它们的非侵入性检测和表征方法。这 项目重点关注巨噬细胞在斑块中的核心作用 形成和去稳定化。目标1将考察以下方面的潜力 地塞米松对斑块进展/消退的影响 单核细胞趋化蛋白-1(MCP-1)的表达 巨噬细胞致动脉粥样硬化产物)诱导突变小鼠模型 通过饮食或血管损伤来治疗。目标2将专注于分子 地塞米松诱导的单核细胞趋化蛋白-1mRNA不稳定性的调节。在《目标3》，一部小说 将建立和研究巨噬细胞的小鼠模型 在选定的时间点进行特定消融以确定其 在斑块进展、消退和重要的破裂中的重要性。 总体而言，这3个项目代表着高度互动的努力 经验丰富的调查人员将开发新的方法来 使用分子生物学、动物模型、临床的易损斑块 调查和核磁共振检查。

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.