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Michaela Artwohl, Thomas Hlzenbein, Clemens Frnsinn, Angelika Freudenthaler, Nicole Huttary, Werner Klaus Waldhusl, Sabina M. Baumgartner-Parzer
Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells
This study evaluated direct effects of peroxisome proliferatoractivated receptor (PPAR) 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 agents structure and ii) endothelial cells vascular origin. Exposure (48 h) of human umbilical vein endothelial cells (HUVECs, n=6) to up to 10 M troglitazone (TRO), rosiglitazone, pioglitazone, and to up to 50 M RWJ241947=MCC-555 (RWJ) inhibited (p<0.05) apoptosis by 825%, whereas 15-deoxy-1214-prostaglandin J2 (PGJ2) triggered (50 M: + 400%, p<0.05) endothelial cell death versus control (=100%). Moreover, RWJ (50 M) completely abrogated TNF-(2000U/ml) and stearic acid (200 M) 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 2539%) 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 PPARagonists 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.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 93, 05/2005
Pages: 810 - 815