Kong Y, Gao Y, Lan D, Zhang Y, Zhan R, Liu M, Zhu Z, Zeng G, Huang Q

Previous study has shown that thiazolidinediones (TZDs) improved endothelium insulin resistance (IR) induced by high glucose concentration (HG)/hyperglycaemia through a PPAR?-dependent-NF?B trans-repression mechanism. However, it is unclear, whether changes in PPAR? expression affect the endothelium IR and what the underlying mechanism is. In the present study, we aimed to address ...

Read More

this issue. HG-treated human umbilical vascular endothelial cells (HUVEC) were transfected by either PPAR?-overexpressing (Ad-PPAR?) or PPAR?-shRNA-containing (Ad-PPAR?-shRNA) adenoviral vectors. Likewise, the rats fed by high-fat diet (HFD) were infected by intravenous administration of Ad-PPAR? or Ad-PPAR?-shRNA. The levels of nitric oxide (NO), endothelin-1 (ET-1) and cytokines (TNF?, IL-6, sICAM-1 and sVCAM-1) and the expression levels of PPAR?, eNOS, AKT, p-AKT, IKK?/? and p-IKK?/? and I?B? were examined; and the interaction between PPAR? and NF?B-P65 as well as vascular function were evaluated. Our present results showed that overexpression of PPAR? notably increased the levels of NO, eNOS, p-AKT and I?B? as well as the interaction of PPAR? and NF?B-P65, and decreased the levels of ET-1, p-IKK?/?, TNF?, IL-6, sICAM-1 and sVCAM-1. In contrast, down-expression of PPAR? displayed the opposite effects. The results demonstrate that the overexpression of PPAR? improves while the down-expression worsens the endothelium IR via a PPAR?-mediated NF?B trans-repression dependent manner. The findings suggest PPAR? is a potential therapeutic target for diabetic vascular complications.

Date: Dec. 01, 2018

View in: Pubmed Google Scholar

227775