Effects of dietary decosahexaenoic acid (DHA) on eNOS in human coronary artery endothelial cells.
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 microM 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 microM). 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 micromol/microg protein/microL). Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation.
Stebbins
Charles L
CL
Department of Internal Medicine, Division of Cardiovascular Medicine, University of California, Davis, CA 95616, USA. clstebbins@ucdavis.edu
Stice
James P
JP
Hart
C Michael
CM
Mbai
Fiona N
FN
Knowlton
Anne A
AA
D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D006152:Cyclic GMP / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology
D018841:HSP90 Heat-Shock Proteins; D042442:Vascular Endothelial Growth Factors; D004281:Docosahexaenoic Acids; C002744:3-nitrotyrosine; D014443:Tyrosine; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP