Sex differences and the role of the renin-angiotensin system in atherosclerosis and abdominal aortic aneurysms

The renin-angiotensin system (RAS) contributes to the development of atherosclerosis and abdominal aortic aneurysms (AAAs). These vascular diseases exhibit sex differences that influence their development, progression, and therapy. Notably, RAS components critical to the synthesis, actions, and catabolism of angiotensin II (AngII) are influenced by sex hormones. In general, estrogen suppresses, while testosterone stimulates the RAS. Sex hormone regulation of the RAS parallels hormone effects on atherosclerosis and AAAs. An emerging area is the role of sex chromosomes to regulate atherosclerosis or AAAs. It is unclear if sex chromosomes regulate vascular diseases by regulating the RAS. However, recent studies demonstrate a striking effect of sex chromosomes on experimental AngII-induced AAAs. Future studies should investigate influences of endogenous and exogenous sex hormones on vascular disease progression. Moreover, future studies should delineate mechanisms for sex chromosome regulation of vascular diseases, and whether these mechanisms are amenable to sex-specific therapies.