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Microvasc Res ; 139: 104252, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34520772

RESUMEN

Soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating antiangiogenic protein, is involved in the pathogenesis of atherosclerosis (AS), and the underlying mechanism is still unclear. Here, we attempted to investigate the mechanism of action of sFlt-1 in AS. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low density lipoprotein (ox-LDL) to induce cell injury. ox-LDL treatment increased LC3-II/LC3-I ratio, Beclin-1 expression and GFP-LC3 puncta in HUVECs, suggesting that ox-LDL may induce autophagic flux impairment in HUVECs. ox-LDL-treated HUVECs displayed a decrease of sFlt-1 levels. Moreover, ox-LDL treatment reduced cell proliferation and elevated apoptosis in HUVECs, which was abrogated by sFlt-1 overexpression. Up-regulation of sFlt-1 repressed the activity of PI3K/AKT/mTOR signaling pathway and enhanced autophagy in HUVECs following ox-LDL treatment. Additionally, sFlt-1 overexpression-mediated increase of autophagy in ox-LDL-treated HUVECs was abolished by 3-methyladenine (autophagy inhibitor). 3-methyladenine abrogated the impact of sFlt-1 overexpression on proliferation and apoptosis in ox-LDL-treated HUVECs. This work confirmed that overexpression of sFlt-1 activated autophagy by repressing PI3K/Akt/mTOR signaling pathway, and thus alleviated ox-LDL-induced injury of HUVECs. Therefore, this study suggests that sFlt-1 may be a potential target for AS treatment.


Asunto(s)
Aterosclerosis/enzimología , Autofagia/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/enzimología , Lipoproteínas LDL/toxicidad , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Apoptosis/efectos de los fármacos , Aterosclerosis/genética , Aterosclerosis/patología , Beclina-1/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Células Endoteliales de la Vena Umbilical Humana/patología , Humanos , Proteínas Asociadas a Microtúbulos/metabolismo , Transducción de Señal , Regulación hacia Arriba , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética
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