Temporal and Spatial Expression of Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Following Myocardial Infarction

Abstract

Following a myocardial infarction (MI), the homeostatic balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is disrupted as part of the left ventricle (LV) response to injury. The full complement of responses to MI has been termed LV remodeling and includes changes in LV size, shape and function. The following events encompass the LV response to MI: (1) inflammation and LV wall thinning and dilation, (2) infarct expansion and necrotic myocyte resorption, (3) accumulation of fibroblasts and scar formation, and (4) endothelial cell activation and neovascularization. In this review, we will summarize MMP and TIMP roles during these events, focusing on the spatiotemporal localization and MMP and TIMP effects on cellular and tissue‐level responses. We will review MMP and TIMP structure and function, and discuss specific MMP roles during both the acute and chronic phases post‐MI, which may provide insight into novel therapeutic targets to limit adverse remodeling in the MI setting.