Metalloproteinases and plasminogen activators in vessel remodeling.
Remodeling of blood vessels underlies the pathogenesis of major cardiovascular disorders, including atherosclerosis, restenosis, and hypertension. Because remodeling of arteries is highly dependent on degradation of the extracellular matrix, which enables cells to migrate and proliferate, there is intense interest in the regulation and the roles of matrix metalloproteinases (MMPs) and the plasminogen activator-plasmin (PA-P) systems in vessel remodeling. Factors that promote vessel remodeling have been shown to be important in upregulating the activities of both proteolytic systems and include chronic changes in hemodynamics, vessel injury, cytokines involved in inflammation, and elevations in reactive oxygen species. The two proteolytic systems utilize common transcription factors to activate their respective genes and are frequently coexpressed in remodeling and atherosclerotic arteries. In this review, we discuss the effects of activating the MMP and PA-P systems on processes involved in vascular remodeling, factors regulating their expression and activation, their roles in restenosis, and the development and progression of atherosclerosis, as well as the ability of currently available inhibitors to prevent unfavorable remodeling and atherosclerosis.
Bobik
Alex
A
Cell Biology Laboratory, Baker Heart Research Institute, PO Box 6492, St Kilda Road Central, Melbourne Victoria 8008, Australia. alex.bobik@baker.edu.au
Tkachuk
Vselovod
V
D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D045726:Metalloproteases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010960:Plasminogen Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D061965:Matrix Metalloproteinase Inhibitors; D014157:Transcription Factors; D045726:Metalloproteases; D010960:Plasminogen Activators