Impaired lipophagy in endothelial cells with prolonged exposure to oxidized low‑density lipoprotein

Abstract

Oxidative stress induces the formation of oxidized low-density lipoprotein (ox-LDL), which accelerates the development of atherosclerosis and the rupture of atherosclerotic plaques by promoting lipid accumulation and inhibiting autophagy in vascular cells. Lipophagy is known to be involved in maintaining the balance of neutral lipid metabolism; however, the phenomenon of lipophagy deficiency in ox-LDL-treated endothelial cells (ECs) remains to be elucidated. It has been demonstrated that lipid accumulation caused by ox-LDL inhibits autophagy, which promotes apoptosis in ECs. The aim of the present study was to investigate the association between decreased autophagy and lipid accumulation in ECs treated with ox-LDL. Electron microscopy demonstrated that the formation of autolipophagosomes was decreased in ox-LDL-treated human umbilical vein ECs compared with that in the LDL-treated group and was accompanied by a decrease in the autophagy-associated proteins via western blotting analysis. Using laser focal colocalization detection, decreased lipid processing was observed in the lysosomes of ox-LDL-treated ECs, which indicated that lipophagy may be attenuated and subsequently result in lipid accumulation in ox-LDL-treated ECs.

OxLDL induces the release of IL-1β from primed human endothelial and smooth muscle cells via different caspase -1-dependent mechanisms

“…It is known that lipids accumulate within VSMC ( 27 ) and EC ( 19 ). We show that significant oxLDL is seen inside cells after priming, suggesting that only ‘activated’ cells (those that express increased scavenger receptors ( 28 )), and not quiescent cells, have the potential to take up oxLDL and release IL-1β.…”

“…Cells were then washed to remove all traces of stimulating cytokines, and the media was replaced with serum-free media (without additional supplements) containing oxLDL (10–50 μg/mL) (Invitrogen) for periods up to 6 h. According to the oxLDL product datasheet, native LDL was isolated from human plasma, which is sourced from a blood bank and tested for HIV, hepatitis B and C, syphilis and other infectious diseases, and subsequently oxidised via a copper sulphate-mediated process to the optimal degree of oxidation. Oil red O staining was used to determine the extent of oxLDL uptake in cells as previously described ( 19 ). It was determined previously that the maximum IL-1β release from HCAEC occurred at 6 h ( 14 ).…”

Extract of high hydrostatic pressure-treated danshen (Salvia miltiorrhiza) ameliorates atherosclerosis via autophagy induction

“…oxLDL induces ECs dysfunction and promotes endothelial lipid accumulation as well as leads to a deficiency of autophagy and accelerates atherosclerosis (20). The impaired autophagy in oxLDL-treated HUVECs was alleviated by HDE treatment (Fig.…”

Shear Stress Alterations Activate BMP4/pSMAD5 Signaling and Induce Endothelial Mesenchymal Transition in Varicose Veins

“…The cells were maintained at 37 °C in 95% humidified air with 5% CO 2 . Endothelial cells were characterized based on von Willebrand factor (vWF) expression [ 15 ] and uptake of acetylated low-density lipoprotein (Ac-LDL) (Invitrogen, USA) [ 16 ].…”