Rosiglitazone attenuates endothelial progenitor cell apoptosis induced by TNF-α via ERK/MAPK and NF-κB signal pathways.

The discovery of endothelial progenitor cells (EPCs) provides us with a novel treatment strategy for complications requiring therapeutic revascularization and vascular repair. However, the feasibility of this strategy may be limited due to reduced number and impaired function of EPCs under stimulation of TNF-α. The present study was designed to investigate the effect of rosiglitazone on EPC apoptosis induced by TNF-α and the molecular mechanisms involved. Rosiglitazone attenuated apoptosis of TNF-α-stimulated EPCs in a dose-dependent manner. Rosiglitazone decreased caspase-3 activity and cleavages of caspase-3, caspase-7, and parp. Rosiglitazone also moderated the dissipation of mitochondrial membrane potential caused by TNF-α treatment and reduced the expression of bax and the release of cytochrome c. Furthermore, rosiglitazone inhibited phosphorylations of ERK/MAPK and NF-κB signal molecules. Both ERK and NF-κB inhibitors decreased TNF-α-induced apoptosis of EPCs, as well as the expression of cleaved caspase-3 and parp. These results suggest that rosiglitazone may mediate the inhibitory effect on EPCs apoptosis under TNF-α stimulation through suppression of ERK/MAPK and NF-κB signal pathways.