Cardiac miRNA profiling in mouse heart failure that is rescued by estrogen treatment .

End-stage heart failure has long been regarded as a terminal state of cardiac pathological remodeling that is almost impossible to be reversed by any available therapies.We discovered that short term estrogen (E2) treatment rescues preexisting severe heart failure (HF) induced by trans-aortic constriction (TAC) in mice by restoring ejection fraction (EF) from 30% to 55% and cardiac fibrosis (Iorga A, Li J, Sharma S, Umar S, Bopassa JC, Nadadur RD, et al. Rescue of Pressure Overload‐Induced Heart Failure by Estrogen Therapy. Journal of the American Heart Association [Internet]). Given the role of microRNAs in wide spectrum of physiological and pathological processes in HF and fibrosis, we explored whether E2 rescues HF and fibrosis by controlling the expression of specific microRNAs (miRs). RNA isolated from cardiac left ventricle of mice in sham (n=4), HF (n=5) and E2-rescued (n=5) groups was sent to Ocean Ridge Biosciences for miR microarray analysis. Comparison of E2-Rescued group versus HF and sham groups revealed a subset of 158 miRs significantly regulated by E2. Healthy mice with an ejection fraction of ˜60% were randomly subjected to sham or transaortic constriction (TAC) surgery as described previously. HF was achieved 6 to 8 weeks after the TAC surgery with an ejection fraction of ˜35%. Once TAC mice reached HF, mice were randomly euthanized (HF group, n=5), or were assigned to treatment of estradiol (E2, n=5) via a subcutaneous 10-day continuous-release pellet of 0.03 mg E2/kg per day (Innovative Research of America,). Sham-operated mice (n=4) served as control.