Matrix metalloproteinases and abdominal aortic aneurysms: a potential therapeutic target.
Abdominal aortic aneurysm (AAA) is a leading cause of death in the United States, and there is no effective treatment in the early course of disease. Therapy to retard or reverse aneurysmal growth requires an understanding of the underlying vascular pathology. Recent research has indicated that enzymatic degradation of structural matrix proteins plays a large role in the formation of AAAs. Specifically, many studies have implicated a family of matrix degrading enzymes, known as matrix metalloproteinases (MMPs), as vital factors in the disease. Although AAA was once thought to be purely secondary to atherosclerosis, investigators have demonstrated various differences between the diseases in both levels and distribution of MMPs, suggesting independent mechanisms. Experimental models have shown that inhibition of these proteinases may slow aortic wall matrix breakdown. The purpose of this article is to review the current literature regarding the role of individual MMPs in AAA, including their complex regulatory mechanisms and possible cellular sources, the importance of MMPs as a potential therapeutic target in the prevention and treatment of AAA, and their inhibition using novel pharmacologic interventions in animal models.
Sinha
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Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
Frishman
W H
WH
D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy / Q000201:enzymology*; D016207:Cytokines / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008264:Macrophages / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000502:physiology; D020782:Matrix Metalloproteinases / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000502:physiology
D016207:Cytokines; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1