Person: Gómez Hernández, María De La Almudena
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First Name
María De La Almudena
Last Name
Gómez Hernández
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
3 results
Search Results
Now showing 1 - 3 of 3
Item 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.Item Concerted regulation of non-alcoholic fatty liver disease progression by microRNAs in apolipoprotein E-deficient mice(Disease Models & Mechanisms, 2021) López-Pastor, Andrea R.; Infante-Menéndez, Jorge; González-Illanes, Tamara; González-López, Paula; González-Rodríguez, Águeda; García-Monzón, Carmelo; Vega de Céniga, Melina; Esparza, Leticia; Gómez Hernández, María De La Almudena; Escribano Illanes, ÓscarThe prevalence of non-alcoholic fatty liver disease (NAFLD) is constantly increasing, and altered expression of microRNAs (miRNAs) fosters the development and progression of many pathologies, including NAFLD. Therefore, we explored the role of new miRNAs involved in the molecular mechanisms that trigger NAFLD progression and evaluated them as biomarkers for diagnosis. As a NAFLD model, we used apolipoprotein E-deficient mice administered a high-fat diet for 8 or 18 weeks. We demonstrated that insulin resistance and decreased lipogenesis and autophagy observed after 18 weeks on the diet are related to a concerted regulation carried out by miR-26b-5p, miR-34a-5p, miR-149-5p and miR-375-3p. We also propose circulating let-7d-5p and miR-146b-5p as potential biomarkers of early stages of NAFLD. Finally, we confirmed that circulating miR-34a-5p and miR-375-3p are elevated in the late stages of NAFLD and that miR-27b-3p and miR-122-5p are increased with disease progression. Our results reveal a synergistic regulation of key processes in NAFLD development and progression by miRNAs. Further investigation is needed to unravel the roles of these miRNAs for developing new strategies for NAFLD treatment.Item 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, ÓscarBackground: 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.