Matrix Metalloproteinases and Abdominal Aortic Aneurysms: A Potential Therapeutic Target

• Published in: Journal of clinical pharmacology Vol. 38; no. 12; pp. 1077 - 1088
• Main Authors: Sinha, Sanjai, Frishman, William H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-12-1998; Sage Science
• Subjects: Aortic Aneurysm, Abdominal - drug therapy; Aortic Aneurysm, Abdominal - enzymology; Biological and medical sciences; Cardiovascular system; Cytokines - physiology; Endothelium, Vascular - cytology; Humans; Macrophages - physiology; Matrix Metalloproteinase 1 - physiology; Matrix Metalloproteinase 2 - physiology; Matrix Metalloproteinase 9 - physiology; Matrix Metalloproteinases - physiology; Medical sciences; Miscellaneous; Muscle, Smooth, Vascular - cytology; Pharmacology. Drug treatments; Tissue Inhibitor of Metalloproteinase-1 - physiology; Stromelysin 1; Enzyme; Pathogenesis; Aneurysm; Cardioprotective agent; Enzyme inhibitor; Cardiovascular disease; Metalloendopeptidases; Review; Biological activity; Gelatinase B; Gelatinase A; Arterial disease; Vascular disease; Prevention; Peptidases; Chemotherapy; Treatment; Animal; Enzymatic digestion; Hydrolases; Aorta; Aortic disease; Interstitial collagenase
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/009127009803801201

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.