Saturated, but Not Unsaturated, Fatty Acids Induce Apoptosis of Human Coronary Artery Endothelial Cells via Nuclear Factor-κB Activation
- Katrin Staiger1,
- Harald Staiger1,
- Cora Weigert1,
- Carina Haas1,
- Hans-Ulrich Häring1 and
- Monika Kellerer12
- 1Division of Endocrinology, Metabolism, and Pathobiochemistry, Department of Internal Medicine, Eberhard-Karls University Tübingen, Tübingen, Germany
- 2Clinic of Diabetology, Endocrinology, Intensive Care Medicine, Vascular Medicine, and Cardiology, Center for Internal Medicine I, Marienhospital Stuttgart, Stuttgart, Germany
- Address correspondence and reprint requests to Dr. Monika Kellerer, Internal Medicine IV, Medical Clinic, University of Tübingen, Otfried-Müller-Str. 10, D-72076 Tübingen, Germany. E-mail: monikakellerer{at}vinzenz.de
Abstract
High nonesterified fatty acid (NEFA) concentrations, as observed in the metabolic syndrome, trigger apoptosis of human umbilical vein endothelial cells. Since endothelial apoptosis may contribute to atherothrombosis, we studied the apoptotic susceptibility of human coronary artery endothelial cells (HCAECs) toward selected NEFAs and the underlying mechanisms. HCAECs were treated with single or combined NEFAs. Apoptosis was quantified by flow cytometry, nuclear factor κB (NFκB) activation by electrophoretic mobility shift assay, and secreted cytokines by enzyme-linked immunosorbent assay. Treatment of HCAECs with saturated NEFAs (palmitate and stearate) increased apoptosis up to fivefold (P < 0.05; n = 4). Unsaturated NEFAs (palmitoleate, oleate, and linoleate) did not promote apoptosis but prevented stearate-induced apoptosis (P < 0.05; n = 4). Saturated NEFA-induced apoptosis neither depended on ceramide formation nor on oxidative NEFA catabolism. However, NEFA activation via acyl-CoA formation was essential. Stearate activated NFκB and linoleate impaired stearate-induced NFκB activation. Pharmacological inhibition of NFκB and inhibitor of κB kinase (IKK) also blocked stearate-induced apoptosis. Finally, the saturated NEFA effect on NFκB was not attributable to NEFA-induced cytokine production. In conclusion, NEFAs display differential effects on HCAEC survival; saturated NEFAs (palmitate and stearate) are proapoptotic, and unsaturated NEFAs (palmitoleate, oleate, and linoleate) are antilipoapoptotic. Mechanistically, promotion of HCAEC apoptosis by saturated NEFA requires acyl-CoA formation, IKK, and NFκB activation.
- HCAEC, human coronary artery endothelial cell
- HUVEC, human umbilical vein endothelial cell
- IKK, inhibitor of κB kinase
- IL, interleukin
- NEFA, nonesterified fatty acid
- NFκB, nuclear factor κB
- TNF, tumor necrosis factor
Footnotes
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K.S. and H.S. contributed equally to this work.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted August 15, 2006.
- Received February 9, 2006.
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