Extracellular matrix remodeling following myocardial injury.
While current therapeutic strategies restore blood flow to the ischemic myocardium and limit infarct size, adverse left ventricular (LV) remodeling that progresses to dysfunction remains a significant complication following myocardial infarction (MI). The extracellular matrix (ECM) is a key component in the remodeling process, and increases in collagen occur in the infarct area to replace necrotic myocytes and form a scar. The ECM is coupled to the cell through cell surface receptors, primary of which are the integrins. In addition, the matrix metalloproteinases coordinate ECM turnover through degradation of ECM components. Several laboratories have demonstrated matrix metalloproteinase (MMP) participation in remodeling events that lead to LV dilation, and inhibition or targeted deletion of specific MMPs has beneficial effects post-MI. MMP inhibition is a particular focus of recent studies designed to understand the underlying mechanisms of LV remodeling and to evaluate pharmacologic strategies that target the ECM to affect adverse LV remodeling following MI.
Lindsey
Merry L
ML
Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA. lindseml@musc.edu
Mann
Douglas L
DL
Entman
Mark L
ML
Spinale
Francis G
FG
D003331:Coronary Vessels / Q000502:physiology; D004108:Dilatation, Pathologic; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology; D009203:Myocardial Infarction / Q000503:physiopathology*; D009206:Myocardium; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
D016326:Extracellular Matrix Proteins; D016023:Integrins; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases