Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches.
A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.
Schulz
Richard
R
Cardiovascular Research Group, Departments of Pediatrics and Pharmacology, University of Alberta, Edmonton, Alberta, Canada. richard.schulz@ualberta.ca
D000818:Animals; D006168:Guinea Pigs; D006331:Heart Diseases / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D012518:Sarcomeres / Q000201:enzymology; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology*; D019210:Troponin I / Q000502:physiology
D061965:Matrix Metalloproteinase Inhibitors; D018994:Myosin Light Chains; D019714:Tissue Inhibitor of Metalloproteinases; D019210:Troponin I; C076659:myosin light chain I; D020778:Matrix Metalloproteinase 2