Treatment with the estrogen receptor beta agonist DPN significantly improved ejection fraction in mice with severe heart failure to 45.3%, whereas the estrogen receptor alpha agonist PPT had no significant effect.
Does estrogen receptor beta activation improve ejection fraction in male mice with severe heart failure?
Estrogen rescues pre-existing severe heart failure in mice primarily through estrogen receptor beta activation, which improves ejection fraction, reduces fibrosis, and stimulates angiogenesis.
Tasa de eventos absoluta: 45.3% vs 31.1%
valor p: p=<0.001
BACKGROUND: Recently, we showed that exogenous treatment with estrogen (E2) rescues pre-existing advanced heart failure (HF) in mice. Since most of the biological actions of E2 are mediated through the classical estrogen receptors alpha (ERα) and/or beta (ERβ), and both these receptors are present in the heart, we examined the role of ERα and ERβ in the rescue action of E2 against HF. METHODS: Severe HF was induced in male mice by transverse aortic constriction-induced pressure overload. Once the ejection fraction (EF) reached ~ 35%, mice were treated with selective agonists for ERα (PPT, 850 μg/kg/day), ERβ (DPN, 850 μg/kg/day), or E2 (30 μg/kg/day) together with an ERβ-antagonist (PHTPP, 850 μg/kg/day) for 10 days. RESULTS: EF of HF mice was significantly improved to 45.3 ± 2.1% with diarylpropionitrile (DPN) treatment, but not with PPT (31.1 ± 2.3%). E2 failed to rescue HF in the presence of PHTPP, as there was no significant improvement in the EF at the end of the 10-day treatment (32.5 ± 5.2%). The improvement of heart function in HF mice treated with ERβ agonist DPN was also associated with reduced cardiac fibrosis and increased cardiac angiogenesis, while the ERα agonist PPT had no significant effect on either cardiac fibrosis or angiogenesis. Furthermore, DPN improved hemodynamic parameters in HF mice, whereas PPT had no significant effect. CONCLUSIONS: E2 treatment rescues pre-existing severe HF mainly through ERβ. Rescue of HF by ERβ activation is also associated with stimulation of cardiac angiogenesis, suppression of fibrosis, and restoration of hemodynamic parameters.
Iorga et al. (Tue,) conducted a other in Heart failure. Diarylpropionitrile (DPN, ER beta agonist) vs. PPT (ER alpha agonist) or untreated heart failure was evaluated on Ejection fraction (EF) (p=<0.001). Treatment with the estrogen receptor beta agonist DPN significantly improved ejection fraction in mice with severe heart failure to 45.3%, whereas the estrogen receptor alpha agonist PPT had no significant effect.