GLI1-mediated pulmonary artery smooth muscle cell pyroptosis contributes to hypoxia-induced pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a clinically common malignant cardiovascular disease. Pyroptosis is a new form of inflammatory cell death that is involved in many disease processes. Glioma-associated oncogene family zinc finger 1 (GLI1) is a transcriptional activator that participates in many diseases, but its role has never been explored in inducing pyroptosis and the progress of PH. In this study, we used an animal model and cell molecular biology to determine the effect of GLI1 on chronic hypoxia-mediated PH progression and pulmonary artery smooth muscle cell (PASMC) pyroptosis. The major findings of the present study are as follows: Hypoxia induced aberrant expression of GLI1. The inhibition of GLI1 attenuated hypoxia-induced PH and PASMC pyroptosis. Meanwhile, GLI1 enhanced apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression by binding with its promoter. GLI1 may promote PASMC pyroptosis through ASC to affect the progression of PH. These findings may identify novel targets for molecular therapy of PH.