Potential protective role of let-7d-5p in atherosclerosis progression reducing the inflammatory pathway regulated by NF-κB and vascular smooth muscle cells proliferation.

Autor: Aroca-Esteban J; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Souza-Neto FV; Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain., Aguilar-Latorre C; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Tribaldo-Torralbo A; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., González-López P; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Ruiz-Simón R; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Álvarez-Villareal M; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain., Ballesteros S; Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain., de Ceniga MV; Department of Angiology and Vascular Surgery, Hospital of Galdakao-Usansolo, Galdakao, Bizkaia, Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Bizkaia, Spain., Landete P; Departmento de Neumología, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Madrid, Spain; Faculty of Medicine, Autonoma University of Madrid, Madrid, Spain., González-Rodríguez Á; Instituto de Investigaciones Biomédicas Alberto Sols (Centro Mixto CSIC-UAM), Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain., Martín-Ventura JL; IIS-Fundation Jimenez-Diaz, Autonoma University of Madrid and CIBERCV, Madrid, Spain., de Las Heras N; Physiology Department, School of Medicine, Complutense University of Madrid, Madrid, Spain., Escribano Ó; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: oescriba@ucm.es., Gómez-Hernández A; Hepatic and Vascular Diseases Laboratory, Biochemistry and Molecular Biology Department, School of Pharmacy, Complutense University of Madrid, Madrid, Spain. Electronic address: algomezh@ucm.es.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Oct; Vol. 1870 (7), pp. 167327. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1016/j.bbadis.2024.167327
Abstrakt: The prevalence of cardiovascular diseases (CVDs) is increasing in the last decades, even is the main cause of death in first world countries being atherosclerosis one of the principal triggers. Therefore, there is an urgent need to decipher the underlying mechanisms involved in atherosclerosis progression. In this respect, microRNAs dysregulation is frequently involved in the progression of multiple diseases including CVDs. Our aim was to demonstrate that let-7d-5p unbalance could contribute to the pathophysiology of atherosclerosis and serve as a potential diagnostic biomarker. We evaluated let-7d-5p levels in vascular biopsies and exosome-enriched extracellular vesicles (EVs) from patients with carotid atherosclerosis and healthy donors. Moreover, we overexpressed let-7d-5p in vitro in vascular smooth muscle cells (VSMCs) to decipher the targets and the underlying mechanisms regulated by let-7d-5p in atherosclerosis. Our results demonstrate that let-7d-5p was significantly upregulated in carotid plaques from overweight patients with carotid atherosclerosis. Moreover, in EVs isolated from plasma, we found that let-7d-5p levels were increased in carotid atherosclerosis patients compared to control subjects specially in overweight patients. Receiver Operating Characteristic (ROC) analyses confirmed its utility as a diagnostic biomarker for atherosclerosis. In VSMCs, we demonstrated that increased let-7d-5p levels impairs cell proliferation and could serve as a protective mechanism against inflammation by impairing NF-κB pathway without affecting insulin resistance. In summary, our results highlight the role of let-7d-5p as a potential therapeutic target for atherosclerosis since its overexpression induce a decrease in inflammation and VSMCs proliferation, and also, as a novel non-invasive diagnostic biomarker for atherosclerosis in overweight patients.
Competing Interests: Declaration of competing interest The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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