Matrix metalloproteinases and atherosclerosis.
Atherosclerosis is a major cause of coronary heart disease, and matrix metalloproteinases (MMPs) play an important role in atherosclerosis by degrading the extracellular matrix, which results in cardiovascular remodeling. Recent studies have identified enhanced expression of MMPs in the atherosclerotic lesion and their contribution to weakening of the vascular wall by degrading the extracellular matrix. The transcription, enzyme processing, and specific inhibition of MMPs by tissue inhibitors of matrix metalloproteinase (TIMPs) regulate these effects. These processes are also modified by inflammatory cytokines and cell-cell contact signaling. Both animal experiments and clinical sample analysis have shown that balance in expression and activation of MMPs and inhibition by TIMPs is critical for the development of stenotic and aneurysmal change. Polymorphism in the MMP gene promoter contributes to inter-individual differences in susceptibility to coronary heart disease. The development of therapeutic drugs specifically targeting MMPs may thus be useful for the prevention of atherosclerotic lesion progression, plaque rupture, and restenosis.
Watanabe
Noboru
N
Shinshu University School of Medicine, Matsumoto, 390-8621, Japan. nwata-sin@umin.ac.jp
Ikeda
Uichi
U
D000818:Animals; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism / Q000627:therapeutic use
D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases