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

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Santos Gomes, J (Author) Other; Mendes Ferreira, P (Author) Other; Adão, R (Author) Other; Maia Rocha, C (Author) Other; Rego, B (Author) Other; Poels, M (Author) Other; Saint Martin Willer, A (Author) Other; Masson, B (Author) Other; Provencher, S (Author) Other; Bonnet, S (Author) Other; Montani, D (Author) Other; Perros, F (Author) Other; Antigny, F (Author) Other; Leite Moreira, F (Author) Other; Brás-Silva C (Author) FMUP

Journal

Title: International Journal Of Molecular Sciences

Vol. 25

Final page: 8054

ISSN: 1661-6596

Publisher: MDPI

Indexing

Scopus - 0 Citations

Other information

Authenticus ID: P-012-PSN

DOI: 10.3390/ijms25158054

Abstract (EN): 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. © 2024 by the authors.

Language: English

Type (Professor's evaluation): Scientific