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Updated: Dec 14, 2025
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
In vivo miR-138-5p inhibition alleviates monocrotaline-induced pulmonary hypertension and normalizes pulmonary KCNK3
Hélène Le Ribeuz1,2,3, Audrey Courboulin1,2,3, Maria-Rosa Ghigna1,2,3
1Faculté de Médecine, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
Background:
The pathogenesis of pulmonary arterial hypertension (PAH) involves many signalling pathways. MicroRNAs are potential candidates involved in simultaneously coordinating multiple genes under such multifactorial conditions.
Methods And Results:
MiR-138-5p is overexpressed in pulmonary arterial smooth muscle cells (PASMCs) from PAH patients and in lungs from rats with monocrotaline-induced pulmonary hypertension (MCT-PH). MiR-138-5p is predicted to regulate the expression of the potassium channel KCNK3, whose loss is associated with the development and progression of PAH. We hypothesized that, in vivo, miR-138-5p inhibition would restore KCNK3 lung expression and subsequently alleviate PAH. Nebulization-based delivery of anti-miR-138-5p to rats with established MCT-PH significantly reduced the right ventricular systolic pressure and significantly improved the pulmonary arterial acceleration time (PAAT). These haemodynamic improvements were related to decrease pulmonary vascular remodelling, lung inflammation and pulmonary vascular cell proliferation in situ. In vivo inhibition of miR-138-5p restored KCNK3 mRNA expression and SLC45A3 protein expression in the lungs.
Conclusions:
We confirmed that in vivo inhibition of miR-138-5p reduces the development of PH in experimental MCT-PH. The possible curative mechanisms involve at least the normalization of lung KCNK3 as well as SLC45A3 expression.
Insights
Inhibiting miR-138-5p in rats with pulmonary hypertension restored KCNK3 expression and improved cardiovascular function. This microRNA targeted KCNK3, offering a potential therapeutic strategy for pulmonary arterial hypertension.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pulmonary Hypertension Pathophysiology
Background:
- Pulmonary arterial hypertension (PAH) pathogenesis involves complex signaling pathways.
- MicroRNAs (miRNAs) are implicated in coordinating gene expression in multifactorial diseases like PAH.
Purpose of the Study:
- To investigate the role of miR-138-5p in pulmonary arterial hypertension (PAH).
- To determine if inhibiting miR-138-5p can restore KCNK3 expression and alleviate PAH in a rat model.
Main Methods:
- Assessed miR-138-5p expression in pulmonary arterial smooth muscle cells (PASMCs) from PAH patients and rat lungs.
- Utilized nebulization to deliver anti-miR-138-5p in a monocrotaline-induced pulmonary hypertension (MCT-PH) rat model.
- Measured hemodynamic parameters, pulmonary vascular remodeling, inflammation, and cell proliferation.
Main Results:
- miR-138-5p was overexpressed in PAH models and predicted to target KCNK3.
- Inhibition of miR-138-5p reduced right ventricular systolic pressure and improved pulmonary arterial acceleration time (PAAT).
- Restored KCNK3 mRNA and SLC45A3 protein expression in rat lungs.
Conclusions:
- In vivo inhibition of miR-138-5p effectively reduces pulmonary hypertension development in an experimental model.
- Therapeutic effects are linked to the normalization of KCNK3 and SLC45A3 expression in the lungs.
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