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Updated: Nov 17, 2025
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Inhibiting miR‑1 attenuates pulmonary arterial hypertension in rats
Yun Liu1, Yong Li2, Jinhai Li1
1Department of Intensive Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
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.
Insights
Inhibiting microRNA-1 (miR-1) in pulmonary arterial hypertension (PAH) rats reduced right ventricle remodeling and fibrosis. This suggests miR-1 plays a role in PAH development and could be a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pulmonary Hypertension Research
Background:
- Pulmonary arterial hypertension (PAH) involves complex molecular mechanisms.
- MicroRNAs (miRs), including miR-1, are implicated in cardiovascular diseases and PAH pathogenesis.
- Right ventricle (RV) remodeling is a critical determinant of outcomes in PAH patients.
Purpose of the Study:
- To investigate the role of miR-1 in the development of RV remodeling and fibrosis in a rat model of PAH.
- To determine if inhibiting miR-1 could ameliorate PAH-induced RV changes.
- To explore the potential involvement of the PI3K/AKT signaling pathway in miR-1's effects.
Main Methods:
- Established PAH in rats using hypoxia and created an in vitro model using cardiac fibroblasts (CFs) under hypoxia.
- Assessed RV remodeling via Masson staining and quantified collagen I, collagen III, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) expression.
- Utilized miR-1 antagomiR transfection to inhibit miR-1 in vivo and in vitro, and analyzed PI3K/AKT pathway activation.
Main Results:
- miR-1 expression was upregulated in the RV and CFs of PAH model rats.
- miR-1 inhibition in PAH rats reversed pulmonary arterial pressure increases and reduced RV hypertrophy and fibrosis.
- Inhibition of miR-1 downregulated fibrotic markers (collagen I, III, α-SMA, CTGF) and suppressed PI3K/AKT pathway activation in RV tissue and CFs.
Conclusions:
- Inhibiting miR-1 effectively attenuates RV hypertrophy and fibrosis in a rat model of PAH.
- The findings suggest that miR-1 contributes to PAH pathogenesis, potentially through the PI3K/AKT signaling pathway.
- Targeting miR-1 presents a potential therapeutic strategy for managing RV dysfunction in PAH.
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