Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches
R Schulz - Annu. Rev. Pharmacol. Toxicol., 2007 - annualreviews.org
Annu. Rev. Pharmacol. Toxicol., 2007•annualreviews.org
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 …
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 …
Abstract
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.
Annual Reviews