Matrix metalloproteinases and atherosclerosis

被引:105
作者
Watanabe N. [1 ]
Ikeda U. [1 ]
机构
[1] Shinshu Univ. School of Medicine
关键词
Atherosclerotic Plaque; Abdominal Aortic Aneurysm; Abdominal Aortic Aneurysm; Carotid Plaque; Arterioscler Thromb Vasc Biol;
D O I
10.1007/s11883-004-0099-1
中图分类号
学科分类号
摘要
Atherosclerosis is a major cause of coronary heart disease and matrix metalloproteinases (MMPs) play an important role in atherosclerosis by degrading the extracellur matrix, which results in cardiovascular remodelling. 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. Copyright © 2004 by Current Science Inc.
引用
收藏
页码:112 / 120
页数:8
相关论文
共 88 条
[1]  
Massova I., Kotra L.P., Mobashery S., Martix Metalloproteinases: Structures, evolution, and diversification, FASEB J., 12, pp. 1075-1095, (1998)
[2]  
Baker A.H., Edwards D.R., Murphy G., Metalloproteinase inhibitors: Biological actions and therapeutic opportunities, J. Cell Sci., 115, pp. 3719-3727, (2002)
[3]  
Creemers E.E., Cleutjens J.P., Smits J.F., Daemens M.J., Matrix metal loproteinase inhibition after myocardial infarction: A new approach to prevent heart failure?, Circ. Res., 89, pp. 201-210, (2001)
[4]  
Visse R., Nagase H., Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry, Circ. Res., 92, pp. 827-839, (2003)
[5]  
Martignetti J.A., Aqeel A.A., Sewairi W.A., Et al., Mutation of the matrix metalloproteinase 2 gene (mmp2) causes a multicentric osteolysis and arthritis syndrome, Nat. Genet., 28, pp. 261-265, (2001)
[6]  
Nagase H., Woessner Jr. J.F., Matrix metalloproteinases, J. Biol. Chem., 274, pp. 21491-21494, (1999)
[7]  
Hojo Y., Ikeda U., Takahashi M., Et al., Matrix metalloproteinase 1 expression by interaction between monocytes and vascular endothelial cells, J. Mol. Cell Cardiol., 32, pp. 1459-1468, (2000)
[8]  
Lijnen H.R., Plasmin and matrix metalloproteinases in vascular remodeling, Thromb Haemost., 86, pp. 324-333, (2001)
[9]  
Rajagopalan S., Meng X.P., Ramasamy S., Et al., Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability, J. Clin. Invest., 98, pp. 2572-2579, (1996)
[10]  
Xu X.P., Meisel S.R., Ong J.M., Et al., Oxidized low-density lipoprotein regulates matrix metalloproteinase-9 and its tissue inhibitors in human macrophages, Circulation, 99, pp. 993-998, (1999)