Portal de investigação
Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Santos-Gomes, J
- Mendes-Ferreira, P
- Adao, R
- Maia-Rocha, C
- Rego, B
- Poels, M
- Willer, AS
- Masson, B
- Provencher, S
- Bonnet, S
- Montani, D
- Perros, F
- Antigny, F
- Brás-Silva, C
Unidades de investigação
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.
Dados da publicação
- ISSN/ISSNe:
- 1661-6596, 1661-6596
- Tipo:
- Article
- Páginas:
- 8054-
- DOI:
- 10.3390/ijms25158054
- Link para outro recurso:
- www.scopus.com
International Journal of Molecular Sciences Multidisciplinary Digital Publishing Institute (MDPI)
Documentos
- Não há documentos
Filiações
Keywords
- miR-146a; pulmonary arterial hypertension (PAH); right ventricular (RV) hypertrophy; right ventricular (RV) failure
Financiamento
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Citar a publicação
Santos J,Mendes P,Adao R,Maia C,Rego B,Poels M,Willer AS,Masson B,Provencher S,Bonnet S,Montani D,Perros F,Antigny F,leite AF,Brás C. Unraveling the Impact of miR-146a in Pulmonary Arterial Hypertension Pathophysiology and Right Ventricular Function. Int. J. Mol. Sci. 2024. 25. (15):p. 8054-8054. IF:5,600. (1).
