title: Delphinidin-3-glucoside protects human umbilical vein endothelial cells against oxidized low-density lipoprotein-induced injury by autophagy upregulation via the AMPK/SIRT1 signaling pathway.
abstract: METHODS
  Oxidized LDL (oxLDL) induced vascular endothelial cell injury is a key event in the pathogenesis of atherosclerosis (AS). In our previous studies, we showed that delphinidin-3-glucoside (Dp), a natural anthocyanin, attenuated oxLDL-induced injury in human umbilical vein endothelial cells (HUVECs), indicating its potential role in preventing AS. However, the involved mechanism is not fully understood.
  
  
  RESULTS
  Via methyl thiazolyl tetrazolium and flow cytometry assay, we found that Dp-attenuated oxLDL-induced cell viability decrease and apoptosis in HUVECs. Depending on confocal microscopy, transmission electron microscopy, and Western blot assay, we found that Dp-induced autophagy in HUVECs, whereas suppression of autophagy significantly abolished the protective role of Dp against oxLDL-induced endothelial cell injury. Furthermore, Dp upregulated sirtuin 1 (SIRT1) expression and SIRT1 knockdown notably suppressed Dp-induced autophagy in HUVECs. Dp also increased the expression of phosphorylated adenosine monophosphate-activated protein kinase, while adenosine monophosphate-activated protein kinase (AMPK) knockdown remarkably abolished Dp-induced SIRT1 expression and subsequent autophagy.
  
  
  CONCLUSIONS
  Our data suggested that Dp protected HUVECs against oxLDL-induced injury by inducing autophagy via the adenosine monophosphate-activated protein kinase/SIRT1 signaling pathway. This new finding might shed light to the prevention and therapy of AS.
authors.affiliation: Chongqing Key Laboratory of Nutrition and Food Safety, Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Mingliang
authors.initials: M
authors.lastname: Chen
authors.forename: Long
authors.initials: L
authors.lastname: Yi
authors.forename: Hui
authors.initials: H
authors.lastname: Chang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Wanqiang
authors.initials: W
authors.lastname: Ma
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Mantian
authors.initials: M
authors.lastname: Mi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000872:Anthocyanins / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001343:Autophagy; D002470:Cell Survival; D002478:Cells, Cultured; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D005960:Glucosides / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008077:Lipoproteins, LDL / Q000009:adverse effects / Q000037:antagonists & inhibitors*; D046529:Microscopy, Electron, Transmission; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D000975:Antioxidants; D005960:Glucosides; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; C099252:oxidized low density lipoprotein; C494120:delphinidin 3-O-glucopyranoside; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Atherosclerosis; Autophagy; Delphinidin-3-glucoside; Endothelial cells; Injury