PIO, a synthetic ligand for PPARã, 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 PPARãLow-HUVECs that we first injured with HG (33 mmol·L-1) were first pretreated with 10 ìmol·L-1 of GW9662 for 30 min, and then treated the cells with different concentrations of PIO (5, 10, or 20 ìmol·L-1) for 24 h. Finally, we measured the levels of NO, ET1, TNFá, and IL6 in the cell culture supernatant. These cells were then used to determine cell viability, caspase3 activity, the levels of IKKá/â mRNA, IKKá/â, and NFêB-p65. Severe dysfunction and activation of IKKá/â-NFêB signaling occurred after we exposed HUVECs to HG. Conversely, treatment with PIO significantly attenuated the dysfunction and the activation of IKKá/â-NFêB signaling induced by HG in a dose-dependent manner. Moreover, the protective effects of PIO were completely abrogated by GW9662 or down-regulation of PPARã. Taken together, the results indicate that PIO protects HUVECs against the HG-induced dysfunction through the inhibition of IKKá/â-NFêB signaling mediated by PPARã.
Active Transport, Cell Nucleus Caspase 3