Deletion of Endothelial Estrogen Receptor Alpha Reduces Arterial Stiffness in Angiotensin II infused-Female Mice

Abstract

Vascular stiffness is a naturally occurring phenomenon associated with aging, but conditions such as obesity and type 2 diabetes accelerate its development, particularly in women. The presence of vascular stiffness increases significantly the risk of cardiovascular disease (CVD). Under physiological conditions, estrogen signaling via estrogen receptor alpha (ERα) increases bioavailable nitric oxide in the endothelium and decreases stiffness. Nevertheless, large clinical trials have failed to demonstrate beneficial cardiovascular effects of estrogen therapy. Our previous work has shown that under conditions of over-nutrition, the lack of ERα ameliorates arterial stiffening in obese and insulin resistant females. Given the central role that activation of the Renin-Angiotensin-System (RAS) has in the pathogenesis of CVD, in the present study we examine the effect of an Angiotensin II (Ang II) infusion in female mice lacking endothelial cell (EC).