Female, but not male, rats with a loss-of-function mutation in estrogen receptor-alpha displayed right ventricular-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload.
Does loss of estrogen receptor-α (ERα) exacerbate right ventricular diastolic dysfunction and fibrosis following pressure overload in rats?
Estrogen receptor-α plays a critical, sex-specific role in protecting the female right ventricle from maladaptive remodeling, diastolic dysfunction, and fibrosis during pressure overload.
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.
Cheng et al. (Fri,) conducted a other in Right ventricular pressure overload (n=38). Loss-of-function mutation in estrogen receptor-alpha (ERaMut) vs. Wild-type (WT) littermates was evaluated on Right ventricular-pulmonary vascular coupling (Ees/Ea) and diastolic function (Tau Weiss). Female, but not male, rats with a loss-of-function mutation in estrogen receptor-alpha displayed right ventricular-vascular uncoupling, diastolic dysfunction, and fibrosis following pressure overload.