Genistein Therapy Reverses Lung Inflammation And Fibrosis During Severe Pulmonary Hypertension Through Estrogen Receptor Beta

Pulmonary Hypertension (PH) is a disease of increasing pulmonary arterial pressure characterized by extensive lung inflammation and fibrosis. We have previously shown that Genistein, a soy isoflavone, can rescue severe PH. Since Genistein is a selective Estrogen Receptor Beta agonist, here we examined whether Genistein can reverse fibrosis and inflammation induced by PH via an Estrogen Receptor Beta dependent mechanism. PH was established by treating male rats with monocrotaline (MCT, 60mg/kg, s.c.). At day 21 when severe PH was established, rats were treated with 10 day Genistein therapy (Gen group), Genistein therapy in the presence of selective Estrogen Receptor β antagonist PHTPP (Gen+PHTPP group), or were left untreated to develop right ventricular failure (RVF group). RVF animals developed severe pulmonary hypertension (RVP=72.96±1.39mmHg vs 31.15±0.56 mmHg in CTRL; RVEF=28.76±0.79% vs 66.22±1.40% in CTRL, all p