Inhibiting miR‑1 attenuates pulmonary arterial hypertension in rats

Liu,Yun; Li,Yong; Li,Jinhai; Zuo,Xiangrong; Cao,Quan; Xie,Weiping; Wang,Hong

doi:10.3892/mmr.2021.11922

Inhibiting miR‑1 attenuates pulmonary arterial hypertension in rats

Authors:
- Yun Liu
- Yong Li
- Jinhai Li
- Xiangrong Zuo
- Quan Cao
- Weiping Xie
- Hong Wang
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Affiliations: Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: February 18, 2021 https://doi.org/10.3892/mmr.2021.11922
Article Number: 283
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRs) are reported to serve key roles in pulmonary arterial hypertension (PAH). miR‑1 has been found in cardiovascular diseases. The present study aimed to determine whether the knockdown of miR‑1 could inhibit right ventricle (RV) remodeling and thereby control PAH in model rats. PAH model rats were established by exposing rats to hypoxia, while cardiac fibroblasts (CFs) obtained from PAH model rats were treated with hypoxia to establish an in vitro model, and RV remodeling was evaluated by Masson staining and the levels of collagen I, collagen III, α‑smooth muscle actin (α‑SMA) and connective tissue growth factor (CTGF) evaluated by western blotting or reverse transcription‑quantitative PCR. The results revealed that the expression levels of miR‑1 were upregulated in the RV of PAH model rats induced with hypoxia and in the CFs treated with hypoxia. The mean pulmonary arterial pressure, RV systolic pressure, RV/(left ventricle + interventricular septum) and RV/tibia length were increased in PAH rats; however, the increases in all parameters were subsequently reversed by transfection with a miR‑1 antagomiR in PAH model rats. The transfection with the miR‑1 antagomiR inhibited the development of RV fibrosis and downregulated the mRNA expression levels of collagen I, collagen III, α‑SMA and CTGF in the RV tissue of PAH model rats. The upregulation of collagen I, collagen III, α‑SMA and CTGF expression levels in hypoxia‑treated CFs was also subsequently reversed by miR‑1 antagomiR transfection. The expression levels of collagen I, collagen III, α‑SMA and CTGF were also upregulated in the CFs obtained from PAH model rats, and these increases were attenuated by miR‑1 antagomiR transfection. The expression levels of phosphorylated (p)‑PI3K and p‑AKT were also upregulated in hypoxia‑treated CFs, and these increases were also inhibited by transfection with miR‑1 antagomiR. In conclusion, these results indicated that inhibiting miR‑1 may attenuate RV hypertrophy and fibrosis in PAH model rats, a mechanism that may involve the PI3K/AKT signaling pathway.

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