The autophagy-lysosome pathway: a novel mechanism involved in the processing of oxidized LDL in human vascular endothelial cells.
Oxidized low-density lipoprotein (ox-LDL) is involved in the pathogenesis of atherosclerosis and atherosclerotic plaque rupture by promoting lipid accumulation, proinflammatory responses, and cell death. LDL is mainly oxidized in the subendothelial layer of the vascular wall and then can be taken up by vascular endothelial cells. However, little is known about the intracellular processing of the damaged LDL. Previous studies found that autophagy is involved in degrading oxidized proteins under oxidative stress conditions in Arabidopsis thaliana, while ox-LDL can activate autophagy in EA.hy926 endothelial cells, suggesting a possible role of autophagy in the degradation of ox-LDL by endothelial cells. The present study showed that ox-LDL aggregated in human umbilical vein endothelial cells (HUVECs) and brought about an increase in the formation of autophagosomes and autolysosomes. Ox-LDL-induced increase in the autophagic level was blocked by treatment with the autophagy inhibitor 3-methyladenine and increased by the autophagy inducer rapamycin, while the aggregation of Dil-labled ox-LDL was increased by 3-methyladenine and decreased by rapamycin. In addition, Dil-labeled ox-LDL colocalized with the autophagy marker MDC, microtubule-associated protein light chain 3 (MAP1-LC3), and lysosome-associated membrane protein 2a (lamp2a). HUVECs treated with Dil-labeled-ox-LDL showed a much greater degree of overlap of MAP1-LC3 and Lamp2a than control. The results suggest that ox-LDL activates the autophagic lysosome pathway in HUVECs through the LC3/beclin1 pathway, leading to the degradation of ox-LDL.
Zhang
Yan-Lin
YL
Department of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Cao
Yong-Jun
YJ
Zhang
Xia
X
Liu
Hui-Hui
HH
Tong
Tong
T
Xiao
Guo-Dong
GD
Yang
Ya-Ping
YP
Liu
Chun-Feng
CF
D001343:Autophagy; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D020123:Sirolimus