title: SIRT1 regulates accumulation of oxidized LDL in HUVEC via the autophagy-lysosomal pathway.
abstract: Autophagy is involved in the degradation of oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs). Sirtuin1 (SIRT1), a new anti-atherosclerotic factor, can induce autophagy in cardiac myocytes. In the present study, we observed the effect of SIRT1 on the accumulation of ox-LDL in HUVECs, and elucidated whether its effect is relative with the autophagy-lysosomal pathway. The results showed that treatment with either SIRT1 siRNA or SIRT1 inhibitor nicotinamide (NAM) increased Dil-labelled-ox-LDL (Dil-ox-LDL) accumulation in HUVECs, and the SIRT1 inducer resveratrol (RSV) decreased it. Knockdown of autophagy-related protein 5 or inhibit the lysosomal degradation by chloroquine (CQ) decreased the effect of RSV. In HUVECs with ox-LDL, expression of LC3II and LC3 puncta was decreased by treatment with SIRT1 siRNA or NAM, but increased by RSV treatment; sequestosome 1 p62 expression showed the opposite effects. Moreover, Dil-ox-LDL combined with SIRT1 siRNA or NAM showed a much smaller degree of overlap of Lamp1 or Cathepsin D with Dil-ox-LDL than in cells with Dil-ox-LDL alone, and RSV treatment resulted in a greater degree of overlap. These results suggest that SIRT1 can decrease the accumulation of ox-LDL in HUVECs, and this effect is related to the autophagy-lysosomal pathway.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: zhangyanlin0012006@163.com.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China. Electronic address: 1531898573@qq.com.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Du
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases & Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases & Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases & Institute of Neuroscience, Soochow University, Suzhou 215123, China. Electronic address: yongjuncao@126.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Cao
mesh_terms: D001343:Autophagy; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D034622:RNA Interference; D000077185:Resveratrol; D000071456:Sequestosome-1 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D000071187:Autophagy-Related Protein 5; D004791:Enzyme Inhibitors; D008077:Lipoproteins, LDL; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D014803:Vitamin B Complex; D009536:Niacinamide; D002738:Chloroquine; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol
keywords: Accumulation; Autophagy-lysosomal pathway; HUVECs; SIRT1; ox-LDL