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MMP Induction and Inhibition in Myocardial Infarction

Abstract

Short-term survival following a myocardial infarction (MI) has greatly improved, due in part to therapeutic interventions that restore blood flow and limit infarct size. The increased incidence of infarct-stimulated left ventricular (LV) remodeling that advances to congestive heart failure (CHF), however, is a significant long-term complication and a leading cause of mortality. Changes to ECM structure and function are primary components of LV remodeling and are precipitated by the early increase in infarct area collagen levels that replace necrotic myocytes and form a scar. ECM turnover is coordinated through the synthesis and degradation of ECM and non-ECM components, particularly the matrix metalloproteinases (MMP), a family of proteolytic enzymes that cleave ECM. MMPs have multiple roles in remodeling events that lead to LV dilation. The inhibition or targeted deletion of specific MMPs attenuates LV remodeling events post-MI. MMP inhibitors have been used in animal models to delineate LV remodeling mechanisms and to evaluate the pharmacologic potential of targeting the ECM to modify LV remodeling post-MI. This review summarizes the current knowledge and limitations of MMP inhibition in the post-MI myocardium.

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Lindsey, M.L. MMP Induction and Inhibition in Myocardial Infarction. Heart Fail Rev 9, 7–19 (2004). https://doi.org/10.1023/B:HREV.0000011390.44039.b7

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  • myocardial infarction
  • extracellular matrix
  • matrix metalloproteinases
  • MMP inhibition