Effects of Dietary Decosahexaenoic Acid (DHA) on eNOS in Human Coronary Artery Endothelial Cells

• Type of Material: Article
• Authors: Charles L. Stebbins, University of California, Davis; James P. Stice, University of California, Davis; Michael Hart, Emory University; Fiona N. Mbai, University of California, Davis; Anne A. Knowlton, University of California, Davis
• Language: English
• Date: 2008-12-01
• Publisher: SAGE Publications (UK and US)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 Sage Publications.
• Final Published Version (URL): http://dx.doi.org/10.1177/1074248408322470
• Title of Journal or Parent Work: Journal of Cardiovascular Pharmacology and Therapeutics
• ISSN: 1074-2484
• Volume: 13
• Issue: 4
• Start Page: 261
• End Page: 268
• Grant/Funding Information: This work was funded by a Pilot and Feasibility Grant from the UC-Davis Clinical Nutrition Research Unit (NIDDK 35747, Dr. Charles H. Halsted, P.I.); and NIH National Institute of Aging Grant AG19327 (AAK).
• Keywords: phospho-Akt; POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; phospho-eNOS; MOLECULAR-MECHANISMS; 3-nitrotyrosine; SHOCK PROTEINS; Akt kinase; HSP90; FISH-OIL-RICH; SHEAR-STRESS; Cardiovascular System & Cardiology; Cardiac & Cardiovascular Systems; Science & Technology; Life Sciences & Biomedicine; ACTIVATION; cell culture; IN-VIVO; Pharmacology & Pharmacy; NITRIC-OXIDE SYNTHASE; CHRONIC HEART-FAILURE
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Endothelial dysfunction occurs in heart disease and may reduce functional capacity via attenuations in peripheral blood flow. Dietary decosahexaenoic acid (DHA) may improve this dysfunction, but the mechanism is unknown. This study determined if DHA enhances expression and activity of eNOS in cultured human coronary artery endothelial cells (HCAEC). HCAEC from 4 donors were treated with 5 nM, 50 nM, or 1 μM DHA for 7 days to model chronic DHA exposure. A trend for increased expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS was observed with 5 and 50 nM DHA. DHA also enhanced expression of 2 proteins instrumental in activation of eNOS: phospho-Akt (5 and 50 nM) and HSP90 (50 nM and 1 μM). Vascular endothelial growth factor-induced activation of Akt increased NOx in treated (50 nM DHA) versus untreated HCAEC (9.2 ± 1.0 vs 3.3 ± 1.1 μmol/μg protein/μL). Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation.