Open AccessDiabetic HDL Is Dysfunctional in Stimulating Endothelial Cell Migration and Proliferation Due to Down Regulation of SR-BI Expression
Author(s) -
Bing Pan,
Yijing Ma,
Hui Ren,
Yanni He,
Yongyu Wang,
Xiaoyi Lv,
Donghui Liu,
Liang Ji,
Baoqi Yu,
Yuhui Wang,
Y Eugene Chen,
Subramaniam Pennathur,
Jonathan Smith,
George Liu,
Lemin Zheng
Publication year - 2012
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0048530
Subject(s) - medicine , endocrinology , protein kinase b , phosphorylation , umbilical vein , endothelial dysfunction , human umbilical vein endothelial cell , chemistry , biology , microbiology and biotechnology , biochemistry , in vitro
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. Methodology/Principal Findings 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/Significance 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.