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

Department of Internal Medicine, University of California, Davis, clstebbins{at}ucdavis.edu

James P. Stice

Department of Internal Medicine, University of California, Davis

C. Michael Hart, MD

Department of Pulmonary and Critical Care Medicine, Veterans Affairs and Emory University Medical Centers, Decatur, Georgia

Fiona N. Mbai, PhD

Department of Internal Medicine, University of California, Davis

Anne A. Knowlton, MD

Department of Internal Medicine, University of California, Davis, Northern California Veterans Affairs

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 NO_x 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.

Key Words: phospho-eNOS • Akt kinase • phospho-Akt • HSP90 • 3-nitrotyrosine • cell culture

This version was published on December 1, 2008

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 13, No. 4, 261-268 (2008)
DOI: 10.1177/1074248408322470


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