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- Title
Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function.
- Authors
Santos-Gomes, Joana; Mendes-Ferreira, Pedro; Adão, Rui; Maia-Rocha, Carolina; Rego, Beatriz; Poels, Manu; Saint-Martin Willer, Anaïs; Masson, Bastien; Provencher, Steeve; Bonnet, Sébastien; Montani, David; Perros, Frédéric; Antigny, Fabrice; Leite-Moreira, Adelino F.; Brás-Silva, Carmen
- Abstract
Pulmonary arterial hypertension (PAH) is a chronic disorder characterized by excessive pulmonary vascular remodeling, leading to elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. MicroRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both hallmarks of PAH. This study aimed to investigate the effects of miR-146a through pharmacological or genetic inhibition on experimental PAH and RV pressure overload animal models. Additionally, we examined the overexpression of miR-146a on human pulmonary artery smooth muscle cells (hPASMCs). Here, we showed that miR-146a genic expression was increased in the lungs of patients with PAH and the plasma of monocrotaline (MCT) rats. Interestingly, genetic ablation of miR-146a improved RV hypertrophy and systolic pressures in Sugen 5415/hypoxia (SuHx) and pulmonary arterial banding (PAB) mice. Pharmacological inhibition of miR-146a improved RV remodeling in PAB-wild type mice and MCT rats, and enhanced exercise capacity in MCT rats. However, overexpression of miR-146a did not affect proliferation, migration, and apoptosis in control-hPASMCs. Our findings show that miR-146a may play a significant role in RV function and remodeling, representing a promising therapeutic target for RV hypertrophy and, consequently, PAH.
- Subjects
VASCULAR remodeling; PULMONARY arterial hypertension; VASCULAR smooth muscle; AEROBIC capacity; SYSTOLIC blood pressure; RIGHT ventricular hypertrophy; LUNGS
- Publication
International Journal of Molecular Sciences, 2024, Vol 25, Issue 15, p8054
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms25158054