Wnt/β-catenin signaling pathways mediate monocrotaline-induced pulmonary arterial hypertension via glycolysis in rats

Abstract

Abstract Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Metabolic abnormalities and immune inflammation are deeply involved in pulmonary vascular remodeling and in the formation of PAH. Cumulative evidence indicates that β-catenin and abnormal glucose metabolism play an important role in the development of PAH, but the underlying mechanism is still elusive. To elucidate this mechanism, we first established a rat model of PAH and then treated some rats with a specific β-catenin inhibitor (XAV939). After examining the protein expression of β-catenin, levels of indicators of glucose metabolism, right ventricular pressure (RVSP) and pulmonary artery histopathology, we found that monocrotaline (MCT)-exposed rats had an increase in levels of glycolytic metabolism markers and that this phenomenon could be blocked by β-catenin inhibitors. This study demonstrated that Wnt/β-catenin signaling promotes the inflammatory response involved in pulmonary vascular remodeling and participates in the formation of PAH by regulating glycolysis in macrophages. Inhibition of Wnt/β-catenin signaling pathways could improve the progression of PAH, which may provide novel therapeutic targets for the treatment of PAH.