Estrogen receptor-α prevents right ventricular diastolic dysfunction and fibrosis in female rats
Tik-Chee Cheng, Jennifer L. Philip, Diana M. Tabima, Santosh Kumari, Bakhtiyor Yakubov, Andrea L. Frump, Timothy A. Hacker, Alessandro Bellofiore, Rongbo Li, Xin Sun, Kara N. Goss, Tim Lahm, Naomi C. Chesler
Abstract
Using a novel loss-of-function mutation in estrogen receptor-α (ERα), we demonstrate that female, but not male, ERα mutant rats display right ventricular (RV)-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload, indicating a sex-dependent role of ERα in protecting against adverse RV remodeling. TIMP metallopeptidase inhibitor 1 (Timp1), matrix metalloproteinase 9 (Mmp9), kallikrein-related peptidase 10 ( Klk10), and Jun Proto-Oncogene ( Jun) were identified as potential mediators in ERα-regulated pathways in RV pressure overload.