Person:
Gómez Hernández, María De La Almudena

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First Name
María De La Almudena
Last Name
Gómez Hernández
URI
https://hdl.handle.net/20.500.14352/77750
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2022 - 20232
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Author: Esparza, Leticia × Subject: 577.2 ×

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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
    (International Journal of Molecular Sciences, 2022) 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
    (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.
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    Role of miR‐15a‐5p and miR‐199a‐3p in the inflammatory pathway regulated by NF‐κB in experimental and human atherosclerosis
    (Clinical and Translational Medicine, 2023) González‐López, Paula; Álvarez‐Villarreal, Marta; Ruiz‐Simón, Rubén; Raposo López‐Pastor, Andrea; Vega de Ceniga, Melina; Esparza, Leticia; Martín‐Ventura, José L.; Gómez Hernández, María De La Almudena; Escribano Illanes, Óscar
    Background: Cardiovascular diseases (CVDs) prevalence has significantlyincreased in the last decade and atherosclerosis development is the main trig-ger. MicroRNAs (miRNAs) are non-coding RNAs that negatively regulate geneexpression of their target and their levels are frequently altered in CVDs. Methods: By RT-qPCR, we analysed miR-9-5p, miR-15a-5p, miR-16-5p andmiR-199a-3p levels in aorta from apolipoprotein knockout (ApoE−/−) mice, anexperimental model of hyperlipidemia-induced atherosclerosis, and in humanaortic and carotid atherosclerotic samples. By in silico studies, Western blotanalysis and immunofluorescence studies, we detected the targets of the alteredmiRNAs. Results: Our results show that miR-15a-5p and miR-199a-3p are significantlydecreased in carotid and aortic samples from patients and mice with atheroscle-rosis. In addition, we found an increased expression in targets of both miRNAsthat participate in the inflammatory pathway of nuclear factor kappa B (NF-κB), such as IKKα,IKKβand p65. In human vein endothelial cells (HUVECs)and vascular smooth muscle cells (VSMCs), the overexpression of miR-15a-5p ormiR-199a-3p decreased IKKα,IKKβand p65 protein levels as well as NF-κB acti-vation. On the other hand, miR-15a-5p and miR-199a-3p overexpression reducedox-LDL uptake and the inflammation regulated by NF-κB in VSMCs. Moreover,although miR-15a-5p and miR-199a-3p were significantly increased in exosomes from patients with advanced carotid atherosclerosis, only in the ROC analysesfor miR-15a-5p, the area under the curve was 0.8951 with apvalue of .0028. Conclusions: Our results suggest that the decrease of miR-199a-3p and miR-15a-5p in vascular samples from human and experimental atherosclerosis could beinvolvedintheNF-κBactivationpathway,aswellasinox-LDLuptakebyVSMCs,contributing to inflammation and progression atherosclerosis. Finally, miR-15a-5p could be used as a novel diagnostic biomarker for advanced atherosclerosis.