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- Title
Diabetic HDL Is Dysfunctional in Stimulating Endothelial Cell Migration and Proliferation Due to Down Regulation of SR-BI Expression.
- Authors
Bing Pan; Yijing Ma; Hui Ren; Yubin He; Yongyu Wang; Xiaofeng Lv; Donghui Liu; Liang Ji; Baoqi Yu; Yuhui Wang; Chen, Y. Eugene; Pennathur, Subramaniam; Smith, Jonathan D.; Liu, George; Zheng, Lemin
- 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. 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 (2/2) 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 (2/2) 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.
- Subjects
STEM cell research; INSECTS; OVARIES; DROSOPHILA melanogaster; DROSOPHILA; CELLS; LARVAE
- Publication
PLoS ONE, 2012, Vol 7, Issue 11, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0048530