title: Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1.
abstract: Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox-LDL-induced autophagy dysfunction and RSV-mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox-LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3-II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox-LDL-induced increase in LC3-II protein level. Ox-LDL increased colocalization of GFP and RFP puncta in mRFP-GFP-tandem fluorescent LC3- (tf-LC3-) transfected cells. Moreover, Ox-LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3-II and increased p62 protein degradation. RSV induced RFP-LC3 aggregation more than GFP-LC3 aggregation. RSV restored lysosomal function and promoted Ox-LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox-LDL-induced impaired autophagic flux, and promoted Ox-LDL degradation through the autophagy-lysosome degradation pathway in HUVECs.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Wawa
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Ningbo Number 2 Hospital, Ningbo 315000, China.
authors.forename: Yande
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China; Institute of Neuroscience, Soochow University, Suzhou 215123, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D008077:Lipoproteins, LDL; D013267:Stilbenes; C099252:oxidized low density lipoprotein; D056564:Sirtuin 1; D000077185:Resveratrol