MicroRNA-150 relieves vascular remodeling and fibrosis in hypoxia-induced pulmonary hypertension

摘要

Pulmonary hypertension (PH) is a dangerous disease, featured by pulmonary vascular remodeling. Excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs) plays crucial roles in this process. MicroRNA-150 (miR-150) level has been found to be reduced in patients with PH, and correlated with the poor survival. This study aimed to investigate the beneficial effect of miR-150 on PH in hypoxia-induced rats, PASMCs and PAECs. The results showed that miR-150 level was reduced in the lung tissue and plasma of hypoxia-treated rats. Lentivirus-mediated overexpression of miR-150 restrained hypoxia-induced increase in right ventricular systolic pressure and decrease in cardiac output. Moreover, as assessed by HE staining, hypoxia-induced thickening of vessel wall was relieved by miR-150 up-regulation. Overexpression of miR-150 also suppressed hypoxia-induced formation of collagen fiber, expressions of alpha-SMA, TGF-beta 1, and collagen I in lung tissues and PASMCs. In addition, the excessive proliferation of PASMCs induced by hypoxia was repressed by miR-150 overexpression via AKT/mTOR signaling pathway. Increased NFATc3 expression in response to hypoxia was restrained by miR-150 overexpression in lung tissue and PAMSCs. Finally, miR-150 overexpression inhibited hypoxia-induced proliferation and apoptosis resistance in PAECs. In conclusion, these results indicate that miR-150 protects against hypoxia-induced pulmonary vascular remodeling, fibrosis, abnormal proliferation of PASMCs and PAECs, which suggests miR-150 as a promising therapeutic target for PH.