RT Journal Article
T1 Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation.
A1 Mayoral-Gonzalez, Isabel
A1 Calderon-Sanchez, Eva M
A1 Galeano-Otero, Isabel
A1 Martin-Bornez, Marta
A1 Gutierrez-Carretero, Encarnacion
A1 Fernandez-Velasco, Maria
A1 Domenech, Nieves
A1 Crespo-Leiro, Maria Generosa
A1 Gomez, Ana Maria
A1 Ordoñez-Fernandez, Antonio
A1 Hmadcha, Abdelkrim
A1 Smani, Tarik
K1 Ucn-2
K1 apoptosis
K1 cardiac remodeling
K1 fibrosis
K1 heart failure
K1 ischemia and reperfusion
K1 miRNA
AB Urocortin-2 (Ucn-2) has demonstrated cardioprotective actions 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 upregulation 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. Interestingly, a significant upregulation of Hmox-1 was observed in the ventricle of ischemic patients with heart failure, correlating 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.
PB Cell Press
SN 2162-2531
YR 2022
FD 2022-01-10
LK http://hdl.handle.net/10668/22458
UL http://hdl.handle.net/10668/22458
LA en
NO Mayoral-González I, Calderón-Sánchez EM, Galeano-Otero I, Martín-Bórnez M, Gutiérrez-Carretero E, Fernández-Velasco M, et al. Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation. Mol Ther Nucleic Acids. 2022 Jan 10;27:838-853.
NO The authors thank Eva Sanchez de Rojas de Pedro for her technical help. The graphical abstract was created with Biorender.com (http://biorender.io).This study was co-financed by FEDER Funds [US-1381135], Agencia Estatal de Investigación [PID2019-104084GB-C22/AEI/10.13039/501100011033]; the Institute of Carlos III [PI18/01197; Red TerCel-Grant RD16/0011/0034]; the Andalusia Government [grant number: PI-0193-2018]; and by Agence National de la Recherche [ANR-19-14-0031-01].
DS RISalud
RD Apr 7, 2025