title: 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.
authors.affiliation: Cardiothoracic Surgery, Medical University of South Carolina, 770 MUSC Complex, 114 Doughty Street, Charleston, SC 29425, USA. lindseml@musc.edu
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D003331:Coronary Vessels / Q000502:physiology; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000502:physiology; D009203:Myocardial Infarction / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D011480:Protease Inhibitors / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood / Q000502:physiology; D016276:Ventricular Function; D017725:Ventricular Pressure; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases