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Implication of miR-155-5p and miR-143-3p in the Vascular Insulin Resistance and Instability of Human and Experimental Atherosclerotic Plaque González-López, Paula Ares-Carral, Carla López-Pastor, Andrea R. Infante-Menéndez, Jorge González Illanes, Tamara Vega de Ceniga, Melina Esparza, Leticia Beneit, Nuria Martín-Ventura, José Luis Escribano Illanes, Óscar Gómez Hernández, María De La Almudena 577.2 atherosclerosis miR-155-5p miR-143-3p unstable plaque apoptosis AKT IGF-IIR Biología molecular (Farmacia) Bioquímica (Farmacia) 2302 Bioquímica 2415 Biología Molecular (1) Background: Cardiovascular diseases (CVDs) are the main cause of death in developed countries, being atherosclerosis, a recurring process underlying their apparition. MicroRNAs (miRNAs) modulate the expression of their targets and have emerged as key players in CVDs; (2) Methods: 18 miRNAs were selected (Pubmed and GEO database) for their possible role in promoting atherosclerosis and were analysed by RT-qPCR in the aorta from apolipoprotein E-deficient (ApoE−/−) mice. Afterwards, the altered miRNAs in the aorta from 18 weeks-ApoE−/− mice were studied in human aortic and carotid samples; (3) Results: miR-155-5p was overexpressed and miR-143-3p was downregulated in mouse and human atherosclerotic lesions. In addition, a significant decrease in protein kinase B (AKT), target of miR-155-5p, and an increase in insulin-like growth factor type II receptor (IGF-IIR), target of miR-143-3p, were noted in aortic roots from ApoE−/− mice and in carotid plaques from patients with advanced carotid atherosclerosis (ACA). Finally, the overexpression of miR-155-5p reduced AKT levels and its phosphorylation in vascular smooth muscle cells, while miR-143-3p overexpression decreased IGF-IIR reducing apoptosis in vascular cells; (4) Conclusions: Our results suggest that miR-155-5p and miR-143-3p may be implicated in insulin resistance and plaque instability by the modulation of their targets AKT and IGF-IIR, contributing to the progression of atherosclerosis. Ministerio de Ciencia e Innovación y Universidades (España) Banco Santander Universidad Complutense de Madrid Depto. de Bioquímica y Biología Molecular Fac. de Farmacia TRUE pub 2024-01-17T19:21:42Z 2024-01-17T19:21:42Z 2022-09-06 journal article VoR https://hdl.handle.net/20.500.14352/93718 1661-6596 10.3390/ijms231810253 1422-0067 eng info:eu-repo/grantAgreement/RTI-2018-095098-B100 info:eu-repo/grantAgreement/PID2021-123076OB-I00 info:eu-repo/grantAgreement/PR75/18-21572 info:eu-repo/grantAgreement/AENC1/22-29754 González-López P, Ares-Carral C, López-Pastor AR, Infante-Menéndez J, González Illaness T, Vega De Ceniga M, et al. Implication of miR-155-5p and miR-143-3p in the Vascular Insulin Resistance and Instability of Human and Experimental Atherosclerotic Plaque. IJMS 2022;23:10253. https://doi.org/10.3390/ijms231810253. Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ open access application/pdf MDPI