Intracellular MMP-2: Role in Normal and Diseased Hearts

摘要: Matrix metalloproteinase (MMP)-2 is an abundant protease found in all cells of the heart and well known for its role extracellular matrix remodeling. Its biological actions physiological processes such as angiogenesis development, cardiac pathologies ischemia–reperfusion injury failure, have been significantly expanded, it now understood to specific targets inside myocyte. MMP-2 localizes nucleus, mitochondria, caveolae, especially sarcomere myocytes. 72-kDa directly activated by oxidative stress, peroxynitrite, a mechanism not requiring proteolytic removal propeptide. Studies from our laboratory identified novel intracellular substrates including troponin I, titin, myosin light chain-1, α-actinin, glycogen synthase kinase-3β, poly (ADP-ribose) polymerase. The proteolysis sarcomeric proteins rapidly follows reperfusion ischemic muscle contributes myocardial stunning injury, which can be ameliorated MMP inhibitors. Other are yet discovered, each provides new mechanisms affect contractile function. inhibitors may become therapeutic drugs treatment diseases associated with enhanced stress.