Abstract 18420: Angiotensin II Infusion Provokes Remodeling of the Aortic Valve Tissue in Mice: A Model for Early Non-Calcified Stage of Aortic Sclerosis
Objective: Asymptomatic aortic valve (AV) sclerosis, characterized by thickening of the cusps with accumulation of reactive oxygen species (ROS) and ECM remodeling, is a hallmark of several cardiovascular conditions. Despite its high prevalence, there is a lacking of reliable animal models for early non-calcified stages of aortic sclerosis. Our preliminary data show that infusion of Angiotensin II in mice receiving a Western diet augments atherosclerosis and causes formation of aortic aneurysms (AA). Although AV disease and atherosclerosis are independent dysfunctions, early stages of these conditions share many similarities. We tested, in vivo, whether Ang II infusion would induce changes in aortic valve microstructure.
Methods: Male wild type mice were fed with Western diet and infused with saline (n=5), or Ang II (1 mg/kg/min) (n=15) for 28 days. Echocardiographic and immunohistological analysis were performed on each animal to test AV thickness, ROS accumulation and ECM remodeling.
Results: We reported the development of aortic aneurysms in 54% of the experimental group compared to the controls, independent from changes in blood pressure (FIG 1A). Interestingly, microdissection analysis of the aortic valve of all mice receiving Ang II show increased cusp thickness (FIG 1B) when compared to saline infused mice (p<0.01). Histological and protein quantification analysis also revealed increased ROS (nitrotyrosine staining) in mice cusps (FIG 1C) and ECM remodeling without affecting the mechanical proprieties of the valve.
Conclusion: Here we conclude that our animal model mimics the tissue remodeling of the aortic cusps with increased thickness and accumulation of reactive oxygen species as seen in human pathological samples of aortic sclerosis.
FIG 1. Ang II infusion and AV thickness. (A) Example of Ang II-induced AA, TTE and AA expansion (B) Representative images of H&E of AV cusp ± Ang II with cusp’s thickness (B) Nitrotyrosine staining and quantification.
- © 2013 by American Heart Association, Inc.