MiR‑371b‑5p inhibits endothelial cell apoptosis in monocrotaline‑induced pulmonary arterial hypertension via PTEN/PI3K/Akt signaling pathways.

Abstract

Pulmonary arterial hypertension (PAH) is a clinical hemodynamic syndrome. It is characterized by elevated PA pressure and pulmonary vascular resistance. In the present study, the role of microRNA (miRNA/miR)-371b-5p in monocrotaline-induced PAH and the underlying mechanisms were investigated. In a monocrotaline-induced PAH rat model, gene chip and reverse transcription-quantitative polymerase chain reaction were employed to measure miRNA expression levels. The results revealed that miR-371b-5p was downregulated in PAH rats compared with the control group. In addition, in vitro results demonstrated that an miR-371b-5p inhibitor reduced miR-371b-5p expression levels, increased apoptosis and reduced proliferation of pulmonary arterial endothelial cells (PAECs) in rats with monocrotaline-induced PAH. Furthermore, inhibition of miR-371b-5p induced phosphatase and tensin homolog (PTEN) protein expression and suppressed that of phosphoinositide 3-kinase (PI3K) and phosphorylated (p)-Akt in the PAECs. In addition, VO-OHpic, a PTEN inhibitor, reduced the protein expression levels of PTEN in the PAECs and inhibited the effects of anti-miR-371b-5p on cell apoptosis. In addition, LY294002, a PI3K inhibitor, reduced the PI3K and p-Akt protein expression in the PAECs and reversed the effects of miR-371b-5p overexpression on the apoptosis of PAECs in rats with monocrotaline-induced PAH. Collectively, the results of the present study indicate that, in this animal model of PAH, miR-371b-5p inhibits apoptosis of PAECs via PTEN/PI3K/Akt signaling pathways.