GLUCOCORTICOIDS, MACROPHAGES AND THE VULNERABLE PLAQUE

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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.