epz005687 and Hypertension--Pulmonary

EPZ005687 is a selective inhibiter of methyltransferase EZH2. In this article, we investigated the protective role and mechanism of EPZ005687 in transverse aortic constriction-induced pulmonary arterial hypertension in mice.. We assigned 15 (6-8 weeks old) male balb/c mice to 3 groups randomly: Sham control + DMSO group, TAC + DMSO group, and TAC + EPZ005687 group (10 mg kg. Murine PAH model was successfully created by TAC operation as evidenced by increased RVSBP and hypertrophic right ventricle. Compared with the sham control, TAC-induced PAH markedly upregulated the expression of EZH2 and ROS deposition in lungs in PAH mice. The inhibiter of methyltransferase EZH2, EPZ005687 significantly inhibits the development of TAC-induced PAH in an EZH2-SOD1-ROS dependent manner.. Our data identified that EZH2 serves a fundamental role in TAC-induced PAH, and administration of EPZ005687 might represent a novel therapeutic target for the treatment of TAC-induced PAH.

Topics: Animals; Aorta; Arterial Pressure; Constriction; Disease Models, Animal; Enhancer of Zeste Homolog 2 Protein; Epigenesis, Genetic; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Indazoles; Lung; Male; Mice; Pulmonary Artery; Pyridones; Reactive Oxygen Species; Superoxide Dismutase-1