SummaryThis study evaluated direct effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists, including thiazolidinediones (TZDs), on vascular cell apoptosis and related protein expression to test the hypothesis that these effects are dependent on i) the respective agent’s structure and ii) endothelial cells’ vascular origin. Exposure (48 h) of human umbilical vein endothelial cells (HUVECs, n=6) to up to 10μM troglitazone (TRO), rosiglitazone, pioglitazone, and to up to 50μM RWJ241947=MCC-555 (RWJ) inhibited (p<0.05) apoptosis by 8–25%, whereas 15-deoxy-Δ12–14-prostaglandin J2 (PGJ2) triggered (50μM:+400%, p<0.05) endothelial cell death versus control (=100%). Moreover, RWJ (50μM) completely abrogated TNF-α (2000U/ml) and stearic acid (200μM) induced apoptosis in HUVECs. Similar results were obtained in human adult (saphenous) vein- and aortic endothelial cells, the latter showing no anti-apoptotic response to TRO. In HUVECs, TZDs’ anti-apoptotic effects inversely correlated (r=-0.95, p<0.01) with increased (p<0.05) expression of the apoptosis-inhibitor bcl-2, whereas PGJ2-induced apoptosis was associated with upregulation of c-myc (+447%) and E2F-1 (+339%). Additionally, TZDs (by 25–39%) and PGJ2 (-70%) reduced (p<0.05) expression of heat shock protein 60 (hsp60) showing no correlation with apoptosis (r=0.14, n.s.). Modulation of apoptosis by PPARγ agonists differs in endothelial cells dependent on their vascular origin and the agonists’ structure. Thiazolidinediones’ ability to reduce both, endothelial apoptosis and hsp60 expression could well add to beneficial vascular effects attributed to these oral antidiabetic drugs.
Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract
