Empagliflozin inhibits PASMCs Phenotypic transition via downexpressing SYK and attenuates artery remodeling in MCT-induced pulmonary arterial hypertension
Abstract
Abstract Purpose Pulmonary arterial hypertension (PAH) is a serious cardiovascular disease that ultimately leads to right heart failure and even death due to pulmonary artery remodeling. The purpose of this study was to investigate the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin (EMPA) on rats with PAH and its direct effects on pulmonary artery smooth muscle cells (PASMCs).Methods PAH was induced in rats by injection of monocrotaline (MCT) (40 mg/kg), followed by treatment with EMPA (10 mg/kg/day) or physiological saline alone for four weeks. The effects of EMPA on the structure and function of the heart, pulmonary artery, and right heart were evaluated via echocardiography, histology, and ELISAs. The proliferation, migration, and phenotypic transition of cells in the pulmonary blood vessels were determined through WB. PDGF-BB was applied to stimulate the proliferation and migration of PASMCs, and the effect of EMPA on PASMCs was evaluated using scratch assays, Transwell assays, colony formation assays, and WB. Moreover, the regulation of SYK by EMPA was assessed. Overexpression of SYK and treatment of PASMCs with EMPA were performed to determine the effects of EMPA on proliferation, migration, and phenotypic transformation.Results Cardiac ultrasound, HE staining, Masson staining, and ELISAs revealed that EMPA alleviates pulmonary artery and right ventricular remodeling and dysfunction in rats with PAH. EMPA normalized the hemodynamic parameters and…
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