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- Title
Protective effects of pioglitazone on vascular endothelial cell dysfunction induced by high glucose via inhibition of IKKα/β-NFκB signaling mediated by PPARγ in vitro.
- Authors
Chen, Chunxiang; Peng, Shaorong; Chen, Fanghui; Liu, Lili; Li, Zhouxue; Zeng, Guohua; Huang, Qiren
- Abstract
PIO, a synthetic ligand for PPARγ, is used clinically to treat T2DM. However, little is known about its protective effects on endothelium and the underlying mechanisms. In this study, we sought to investigate the protective effects of PIO on endothelium and its probable mechanisms: 95% confluent wild type (WT) HUVECs and PPARγLow-HUVECs that we first injured with HG (33 mmol·L-1) were first pretreated with 10 μmol·L-1 of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5, 10, or 20 μmol·L-1) for 24 h. Finally, we measured the levels of NO, ET1, TNFα, and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKKα/β mRNA, IKKα/β, and NFκB-p65. Severe dysfunction and activation of IKKα/β-NFκB signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKα/β-NFκB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARγ. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKα/β-NFκB signaling mediated by PPARγ.
- Subjects
PIOGLITAZONE; ENDOTHELIUM; ENDOTHELIAL cells; NITRIC oxide; NITROGEN compounds; THERAPEUTICS
- Publication
Canadian Journal of Physiology & Pharmacology, 2017, Vol 95, Issue 12, p1480
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2016-0574