Artículo
Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation
Autor/es | Mayoral-González, Isabel
Calderón Sánchez, Eva M. Galeano-Otero, Isabel Martín Bórnez, Marta Gutiérrez Carretero, Encarnación Fernández Velasco, María Ordóñez Fernández, José Antonio Smani Hajami, Tarik |
Departamento | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica Universidad de Sevilla. Departamento de Cirugía |
Fecha de publicación | 2022 |
Fecha de depósito | 2022-12-01 |
Publicado en |
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Premios | Premio Mensual Publicación Científica Destacada de la US. Facultad de Medicina |
Resumen | Urocortin-2 (Ucn-2) has demonstrated cardioprotective ac tions against myocardial ischemia-reperfusion (I/R) injuries.
Herein, we explored the protective role of Ucn-2 through
microRNAs (miRNAs) post-transcriptional ... Urocortin-2 (Ucn-2) has demonstrated cardioprotective ac tions against myocardial ischemia-reperfusion (I/R) injuries. Herein, we explored the protective role of Ucn-2 through microRNAs (miRNAs) post-transcriptional regulation of apoptotic and pro-fibrotic genes. We determined that the intravenous administration of Ucn-2 before heart reperfusion in a Wistar rat model of I/R recovered cardiac contractility and decreased fibrosis, lactate dehydrogenase release, and apoptosis. The infusion of Ucn-2 also inhibited the upregula tion of 6 miRNAs in revascularized heart. The in silico analysis indicated that miR-29a and miR-451_1* are predicted to target many apoptotic and fibrotic genes. Accordingly, the transfection of neonatal rat ventricular myocytes with mimics overexpressing miR-29a, but not miR-451_1*, prevented I/R induced expression of pro- and anti-apoptotic genes such as Apaf-1, Hmox-1, and Cycs, as well as pro-fibrotic genes Col-I and Col-III. We also confirmed that Hmox-1, target of miR 29a, is highly expressed at the mRNA and protein levels in adult rat heart under I/R, whereas, Ucn-2 abolished I/R induced mRNA and protein upregulation of HMOX-1. Inter estingly, a significant upregulation of Hmox-1 was observed in the ventricle of ischemic patients with heart failure, corre lating negatively with the left ventricle ejection fraction. Altogether, these data indicate that Ucn-2, through miR-29a regulation, provides long-lasting cardioprotection, involving the post-transcriptional regulation of apoptotic and fibrotic genes. |
Cita | Mayoral-González, I., Calderón Sánchez, E.M., Galeano-Otero, I., Martín Bórnez, M., Gutiérrez Carretero, E., Fernández Velasco, M.,...,Smani Hajami, T. (2022). Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation. Molecular Therapy-Nucleic Acids, 27, 838-853. https://doi.org/10.1016/j.omtn.2022.01.003. |
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