Universidad Complutense de Madrid
E-Prints Complutense

MicroRNA-126 regulates HypoxiaInducible Factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence

Impacto

Downloads

Downloads per month over past year

Alique, Matilde and Bodega, Guillermo and Giannarelli, Chiara and Carracedo, Julia and Ramírez, Rafael (2019) MicroRNA-126 regulates HypoxiaInducible Factor-1α which inhibited migration, proliferation, and angiogenesis in replicative endothelial senescence. Scientific Reports, 9 (1). ISSN 2045-2322

[img]
Preview
PDF
Creative Commons Attribution.

4MB

Official URL: https://www.ncbi.nlm.nih.gov/pubmed/31089163



Abstract

Whereas a healthy endothelium maintains physiological vascular functions, endothelial damage contributes to the development of cardiovascular diseases. Endothelial senescence is the main determinant of endothelial dysfunction and thus of age-related cardiovascular disease. The objective of this study is to test the involvement of microRNA-126 and HIF-1α in a model of replicative endothelial senescence and the interrelationship between both molecules in this in vitro model. We demonstrated that senescent endothelial cells experience impaired tube formation and delayed wound healing. Senescent endothelial cells failed to express HIF-1α, and the microvesicles released by these cells failed to carry HIF-1α. Of note, HIF-1α protein levels were restored in HIF-1α stabilizer-treated senescent endothelial cells. Finally, we show that microRNA-126 was downregulated in senescent endothelial cells and microvesicles. With regard to the interplay between microRNA-126 and HIF-1α, transfection with a microRNA-126 inhibitor downregulated HIF-1α expression in early passage endothelial cells. Moreover, while HIF-1α inhibition reduced tube formation and wound healing closure, microRNA-126 levels remained unchanged. These data indicate that HIF-1α is a target of miRNA-126 in protective and reparative functions, and suggest that their therapeutic modulation could benefit age-related vascular disease.

Resumen (otros idiomas)

Un endotelio sano mantiene las funciones fisiológicas vasculares, mientras que el daño endotelial contribuye al desarrollo de enfermedades cardiovasculares. La senescencia endotelial es la determinante principal de la disfunción endotelial y, por tanto, de las enfermedades cardiovasculares relacionadas con la edad. El objetivo de este estudio fue establecer la participación del microRNA-126 y la molécula Hypoxia-inducible factor 1 (HIF-1) en un modelo de senescencia replicativa inducida en el endotelio. Nuestro trabajo demuestra que HIF-1α es necesario para prolongar la vida útil de las células y está implicado en el mantenimiento de las funciones protectoras y reparadoras de las células endoteliales. La vía del microRNA-126 /HIF-1α juega un papel importante en los mecanismos por los cuales se regula la función endotelial. Estos hallazgos identifican un nuevo mecanismo involucrado en senescencia endotelial replicativa (Figura), y es posible que estas moléculas puedan ser objetivos para su modulación terapéutica para la protección y reparación de las células vasculares en situaciones de envejecimiento o enfermedad vascular.

Item Type:Article
Subjects:Medical sciences > Biology > Genetics
Medical sciences > Biology > Microbiology
ID Code:57490
Deposited On:25 Oct 2019 12:43
Last Modified:25 Oct 2019 12:43

Origin of downloads

Repository Staff Only: item control page