Role of the renin-angiotensin system in the development of abdominal aortic aneurysms in animals and humans.
The mediators for the initiation, progression, and rupture of abdominal aortic aneurysms (AAAs) have not been defined. Recent evidence has demonstrated that chronic infusion of angiotensin II via subcutaneously placed osmotic pumps can reproducibly form AAAs in mice. The evolution of AngII-induced AAAs in these mice is complex. Rapid medial macrophage accumulation precedes transmedial breaks and large lumen expansion, which are restricted to the suprarenal aorta. After this initial phase, there is a more gradual rate of lumen expansion that is progressive with continued AngII exposure. There is extensive aortic remodeling during this gradual expansion phase. An initial prominent thrombus gradually resolves and is replaced by fibrous tissue containing several types of inflammatory cells. At prolonged intervals of AngII infusion, internal aortic diameters of the suprarenal aorta can increase up to fourfold compared to the same region in saline-infused mice. The extrapolation of these data in mice to the development of human AAAs remains to be determined. However, there are a considerable number of drugs available to potentially test the efficacy of inhibiting the renin-angiotensin system on the progression of the human disease.
Daugherty
Alan
A
Cardiovascular Research Center, Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0200, USA. Alan.Daugherty@uky.edu
Rateri
Debra L
DL
Cassis
Lisa A
LA
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D012084:Renin-Angiotensin System
D001057:Apolipoproteins E; D000804:Angiotensin II