Silencing PDK1 limits hypoxia‑induced pulmonary arterial hypertension in mice via the Akt/p70S6K signaling pathway

Di,Ruomin; Yang,Zhongzhou; Xu,Peng; Xu,Yingjia

doi:10.3892/etm.2019.7627

Silencing PDK1 limits hypoxia‑induced pulmonary arterial hypertension in mice via the Akt/p70S6K signaling pathway

Authors:
- Ruomin Di
- Zhongzhou Yang
- Peng Xu
- Yingjia Xu
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Affiliations: Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, P.R. China, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu 210061, P.R. China
Published online on: May 29, 2019 https://doi.org/10.3892/etm.2019.7627
Pages: 699-704

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Abstract

The present study aimed to investigate the effect of phosphoinositide‑dependent protein kinase‑1 (PDK1) on hypoxia‑induced pulmonary arterial hypertension (PAH). A mouse model of hypoxia‑induced PAH was generated using normal or PDK1‑knockout mice. Histological analysis and hemodynamic evaluations were performed to identify the progression of PAH. The expression and phosphorylation of PDK1/protein kinase B (Akt) signaling pathway associated proteins were detected by western blot analysis. Increased lung vessel thickness, right ventricular (RV) systolic pressure (RVSP), RV hypertrophy index (RVHI) values [the RV weight-to-left ventricular (LV) plus septum (S) weight ratio] and PDK1 expression were observed in the hypoxia‑induced PAH model compared with the normal control. The phosphorylation of AktT308, proline‑rich Akt1 substrate 1 (PRAS40) and S6KT229 was also notably increased in the PAH model compared with the control. The changes of proteins were not observed in the hypoxia treated PDK1flox/+: Tie2-Cre mice. Similarly, the RVSP and RVHI values, and PDK1 expression were reduced in the hypoxia treated PDK1flox/+: Tie2-Cre mice to a level comparable with those in the control, suggesting that PDK1 partial knockout significantly limited hypoxia‑induced PAH. The results of the present study indicate that PDK1 is essential for hypoxia‑induced PAH through the PDK1/Akt/S6K signaling cascades.

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