Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells

Michaela Artwohl; Thomas Hölzenbein; Clemens Fürnsinn; Angelika Freudenthaler; Nicole Huttary; Werner Klaus Waldhäusl; Sabina M. Baumgartner-Parzer

doi:10.1160/TH04-09-0615

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(05): 810-815
DOI: 10.1160/TH04-09-0615

Rapid and Short Communication

Schattauer GmbH

Thiazolidinediones inhibit apoptosis and heat shock protein 60 expression in human vascular endothelial cells

Authors

Michaela Artwohl

¹Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism
Thomas Hölzenbein

²Department of Surgery, Division of Vascular Surgery
Clemens Fürnsinn

¹Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism
Angelika Freudenthaler

¹Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism
Nicole Huttary

³Clinical Institute of Pathology, Medical University of Vienna, Austria
Werner Klaus Waldhäusl

¹Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism
Sabina M. Baumgartner-Parzer

¹Department of Internal Medicine III, Clinical Division of Endocrinology and Metabolism

Abstract

Summary

This 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-Δ^12–14-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.

Keywords

Endothelium - PPARγ agonists - thiazolidinediones - apoptosis - heat shock protein 60

Full Text

References

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