Medicine and Health Sciences Commons^™

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …