title: Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.
abstract: BACKGROUND
  Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction.
  
  
  RESULTS
  We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (-/-) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (-/-) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically.
  
  
  CONCLUSIONS
  Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically.
authors.affiliation: The Institute of Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Peking University Health Science Center, Beijing, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pan
authors.forename: Yijing
authors.initials: Y
authors.lastname: Ma
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.forename: Yubin
authors.initials: Y
authors.lastname: He
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Lv
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Ji
authors.forename: Baoqi
authors.initials: B
authors.lastname: Yu
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.forename: Lemin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001011:Aorta / Q000166:cytology; D002465:Cell Movement; D049109:Cell Proliferation; D048909:Diabetes Complications / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis*
chemical_list: D008075:Lipoproteins, HDL; D051122:Scavenger Receptors, Class B; D051057:Proto-Oncogene Proteins c-akt