Article Dans Une Revue International Journal of Molecular Sciences Année : 2024

Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function

J. Santos-Gomes (1) , P. Mendes-Ferreira (1, 2) , R. Adão (1, 3, 4, 5) , C. Maia-Rocha (1) , B. Rego (1) , M. Poels (1) , A. Saint-Martin Willer (6, 7, 2, 8) , B. Masson (8, 7, 2, 6) , S. Provencher (9, 10) , S. Bonnet (9, 10) , D. Montani (11, 12, 2, 8, 7) , F. Perros (13, 2, 12, 7) , F. Antigny (11, 8, 7) , A. F. Leite-Moreira (1) , C. Brás-Silva (1)

Résumé

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.

Dates et versions

inserm-04756436 , version 1 (28-10-2024)

Identifiants

Citer

J. Santos-Gomes, P. Mendes-Ferreira, R. Adão, C. Maia-Rocha, B. Rego, et al.. Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function. International Journal of Molecular Sciences, 2024, 25 (15), pp.8054. ⟨10.3390/ijms25158054⟩. ⟨inserm-04756436⟩
14 Consultations
0 Téléchargements

Altmetric

Partager

More