What has been learned about the cardiovascular effects of matrix metalloproteinases from mouse models?
Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for extracellular protein degradation in the cardiovascular system. Originally known to play pivotal roles in tissue morphogenesis and wound healing, they have been shown to participate in the complex remodeling processes in blood vessels and the myocardium. The biological activity of MMPs is regulated at different levels: (1) gene expression, (2) activation of precursor proenzyme forms by other MMPs or non-MMP proteins, including thrombin and plasmin, (3) complex formation with surface and extracellular matrix (ECM) components and (4) inhibition by endogenous tissue inhibitors of MMPs, the TIMPs. Murine models with gain or loss of gene function of different MMPs and TIMPS have provided a wealth of experimental data on their critical role in pathological conditions ranging from atherosclerosis, vascular injury, and restenosis to left ventricular function and structural remodeling following chronic pressure and volume overload and ischemia-reperfusion injury.
Janssens
Stefan
S
Department of Cardiology, Center for Transgene Technology and Gene Therapy, Flemish Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium. stefan.janssens@med.kuleuven.be
Lijnen
H Roger
HR
D000818:Animals; D002318:Cardiovascular Diseases / Q000201:enzymology*; D002319:Cardiovascular System / Q000201:enzymology*; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000201:enzymology*; D005786:Gene Expression Regulation; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D020257:Ventricular Remodeling
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases