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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/H2178    most recent 00933.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Pfrommer, C. A. Articles by Weber, P. C. Search for Related Content PubMed PubMed Citation Articles by Pfrommer, C. A. Articles by Weber, P. C.

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Regulation of Cardiovascular Functions by Eicosanoids and Other Lipid Mediators

Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis

Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Munich, Germany

Submitted 31 August 2005 ; accepted in final form 8 February 2006

Induction of apoptosis represents a potential reaction of endothelial cells (ECs) after injury of the vascular endothelium. Beneficial effects of n–3 polyunsaturated fatty acids (PUFAs) in vascular diseases are widely recognized although the responsible mechanisms are not fully understood. Because it is not known whether PUFAs modulate EC apoptosis, we investigated the effects of n–3 and n–6 PUFAs on 4-hydroxynonenal (HNE)-induced EC apoptosis by annexin V staining and caspase-3 activation assays. Pretreatment with the n–3 fatty acid docosahexaenoic acid (DHA) reduced HNE-induced EC apoptosis. DHA-treated cells did not show the pronounced drop in intracellular GSH after HNE exposure seen in vehicle- or n–6 arachidonic acid-treated cells. This is most likely due to increased GSH levels in DHA-treated cells. Furthermore, DHA pretreatment increased ciap1 mRNA levels and transfection of cIAP1 small interfering RNA abolished the protective effect of DHA in HNE-induced apoptosis in HUVECs. Thus pretreatment of HUVECs with DHA reduces HNE-induced oxidative stress and apoptosis, and the protective effects of DHA seem to be dependent on cIAP1. The results provide a possible new mechanism for the atheroprotective effects of n–3 fatty acids in vascular disease.

cardiovascular disease; n–3 fatty acids; 4-hydroxynonenal; inhibitor of apoptosis protein; oxidative stress