The role of the renin-angiotensin system in aortic aneurysmal diseases.
The renin-angiotensin system has been invoked in the development of both abdominal and thoracic aortic aneurysms. This has been demonstrated experimentally by the chronic subcutaneous infusion of angiotensin II, which consistently leads to development of abdominal aortic aneurysms (AAAs) in mice. Angiotensin II-induced AAAs have highly heterogenous cellular and extracellular matrix characteristics throughout the aorta that change markedly with infusion duration. The mechanistic basis for the reproducible location of AAA development has not been elucidated, but many insights have been provided, especially regarding receptor and inflammatory mechanisms. A recent clinical study provided limited evidence for extrapolating these results to mechanisms of human AAAs. Experimental evidence has also demonstrated that antagonism of angiotensin II type 1 (AT1) receptors prevents ascending aortic aneurysms in a murine model of Marfan's syndrome. A clinical study is currently ongoing to demonstrate the efficacy of AT1 receptor antagonism in humans.
Lu
Hong
H
Graduate Center for Nutritional Sciences, Wethington Building, Room 521b, 900 South Limestone Street, University of Kentucky, Lexington, KY 40536-0200, USA.
Rateri
Debra L
DL
Cassis
Lisa A
LA
Daugherty
Alan
A
D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000503:physiopathology; D006801:Humans; D051379:Mice; D012084:Renin-Angiotensin System / Q000187:drug effects; D012307:Risk Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D000804:Angiotensin II