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

Aroca-Esteban, Javier; Souza-Neto, Francisco V.; Aguilar-Latorre, Carlota; Tribaldo-Torralbo, Alba; González-López, Paula; Ruiz-Simón, Rubén; Álvarez-Villareal, Marta; Ballesteros, Sandra; Vega de Ceniga, Melina; Landete, Pedro; González-Rodríguez, Águeda; Martín-Ventura, José L; Heras, Natalia de Las; Escribano Illanes, Óscar; Gómez Hernández, María De La Almudena

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

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Aroca-Esteban J BBA Mol Basis of Disease 2024.pdf (3.72 MB)

Official URL

https://doi.org/10.1016/j.bbadis.2024.167327

Publication date

2024

Authors

Aroca-Esteban, Javier

Souza-Neto, Francisco V.

Aguilar-Latorre, Carlota

Tribaldo-Torralbo, Alba

González-López, Paula

Ruiz-Simón, Rubén

Álvarez-Villareal, Marta

Ballesteros, Sandra

Vega de Ceniga, Melina

Landete, Pedro

Publisher

Elsevier

Citations

Exportar

URI

https://hdl.handle.net/20.500.14352/106819

Abstract

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.