Myocardial extracellular matrix remodeling in ischemic heart failure.
Left ventricular (LV) remodeling is a process whereby structural alterations attempt to compensate altered hemodynamic load. In the chronic setting this process becomes maladaptive, self-sustaining and is associated with worsened survival. The extracellular matrix (ECM) of the heart, once believed an inert scaffold for cardiomyocytes, is now known to play an important role in LV remodeling. The enzyme system primarily responsible for ECM turnover is the matrix metalloproteinases (MMPs), and these enzymes are robustly altered in cardiovascular pathologies, including myocardial infarction (MI) and ischemic heart failure. A cause-and-effect relationship has been established between MMPs and LV remodeling post MI, as MMP inhibition prevents LV dilation and preserves cardiac function in animal models of infarction. In spite of this, initial clinical experience with MMP inhibition post MI has been disappointing. This review examines the structural and functional roles of the myocardial ECM, the evidence for MMP involvement in LV remodeling, and recent investigations into MMPs as prognostic markers and therapeutic targets.
Gallagher
Gabrielle L
GL
Cardiac Technology Centre and Kolling Institute, University of Sydney at Royal North Shore Hospital, St Leonards (Sydney) NSW, Australia. ggallagh@nsccahs.health.nsw.gov.au
Jackson
Christopher J
CJ
Hunyor
Stephen N
SN
D000818:Animals; D002303:Cardiac Output, Low / Q000188:drug therapy / Q000201:enzymology*; D005109:Extracellular Matrix / Q000737:chemistry / Q000201:enzymology*; D024022:Fibrillar Collagens / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000201:enzymology*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology*; D020257:Ventricular Remodeling
D024022:Fibrillar Collagens; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases