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

Zhu,Guangfa; Zhang,Wenmei; Liu,Yan; Wang,Shenghao

doi:10.3892/mmr.2018.9614

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

Authors:
- Guangfa Zhu
- Wenmei Zhang
- Yan Liu
- Shenghao Wang
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Affiliations: Department of Pulmonary and Critical Care Medicine, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of Infectious Diseases, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, P.R. China
Published online on: October 31, 2018 https://doi.org/10.3892/mmr.2018.9614
Pages: 5489-5501
Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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