Basic science of abdominal aortic aneurysms: emerging therapeutic strategies for an unresolved clinical problem.
Abdominal aortic aneurysms (AAAs) are an increasingly common and potentially lethal condition. Surgical repair of AAA is now yet performed quite safely, yet ruptured AAAs still carry mortality rates of 50% to 70%. Ultrasound screening may help identify unsuspected AAA, thereby allowing elective repair. Because AAAs too small to warrant operation still expand progressively, therapeutic approaches to suppress AAA growth would be welcome. Current concepts indicate that AAAs arise through pathophysiologic process distinct from occlusive atherosclerosis and dominated by degenerative changes in the elastic media. These include marked alterations in elastin and collagen, chronic inflammation, and features of autoimmunity, medial neovascularization, and a decrease in vascular smooth muscle cells. Proteinases associated with mononuclear inflammatory cells, particularly matrix metalloproteinases, likely mediate the degradation of structural proteins in the aortic wall. Experimental studies demonstrate that similar processes occur in an elastase-induced rodent model of AAA, providing a means by which to develop novel therapeutic strategies for this disease. Pharmacologic inhibitors of matrix metalloproteinases act to suppress aortic elastin degradation and limit the growth of experimental AAA in vivo, suggesting at least one approach that may be useful in clinical application. Further developments can be expected to increase knowledge of the pathophysiology underlying aortic aneurysm disease, ultimately providing new therapies for small AAAs based on sound understanding of disease mechanisms.
Section of Vascular Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
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D000818:Animals; D001012:Aorta, Abdominal; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy; D001019:Aortic Rupture / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male