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Microvasc Res ; 139: 104252, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520772

RESUMO

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.


Assuntos
Aterosclerose/enzimologia , Autofagia/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/enzimologia , Lipoproteínas LDL/toxicidade , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Apoptose/efeitos dos fármacos , Aterosclerose/genética , Aterosclerose/patologia , Proteína Beclina-1/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Proteínas Associadas aos Microtúbulos/metabolismo , Transdução de Sinais , Regulação para Cima , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
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