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

• Published in: American journal of physiology. Heart and circulatory physiology 2006-06, Vol.290 (6), p.H2178-H2186
• Main Authors: Pfrommer, Claudia A, Erl, Wolfgang, Weber, Peter C
• Format: Article
• Language: English
• Subjects: Aldehydes - antagonists & inhibitors; Aldehydes - toxicity; Annexin A5 - metabolism; Apoptosis - drug effects; Blotting, Western; Cell Survival - drug effects; Cells, Cultured; Cytochromes c - metabolism; Docosahexaenoic Acids - pharmacology; Endothelial Cells - drug effects; Flow Cytometry; Glutathione - metabolism; Humans; Inhibitor of Apoptosis Proteins - antagonists & inhibitors; Inhibitor of Apoptosis Proteins - biosynthesis; Inhibitor of Apoptosis Proteins - genetics; Oxidative Stress - drug effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Small Interfering - pharmacology; Stress, Physiological - pathology; Superoxides - metabolism; Transfection
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00933.2005

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 Address for reprint requests and other correspondence: C. A. Pfrommer, Program in Developmental Biology, Hospital for Sick Children Research Institute, Toronto, Ontario, M5G 1L7, Canada (e-mail: claudia.pfrommer{at}utoronto.ca )