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Adenoviral expression of 15-lipoxygenase-1 in rabbit aortic endothelium: role in arachidonic acid-induced relaxation. Am J Physiol Heart Circ Physiol 2007 Feb;292(2):H1033-41 PMID: 17040969

Pubmed ID

17040969

Abstract

Endothelium-dependent vasorelaxation of the rabbit aorta is mediated by either nitric oxide (NO) or arachidonic acid (AA) metabolites from cyclooxygenase (COX) and 15-lipoxygenase (15-LO) pathways. 15-LO-1 metabolites of AA, 11,12,15-trihydroxyeicosatrienoic acid (THETA), and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA) cause concentration-dependent relaxation. We tested the hypothesis that in the 15-LO pathway of AA metabolism, 15-LO-1 is sufficient and is the rate-limiting step in inducing relaxations in rabbit aorta. Aorta and rabbit aortic endothelial cells were treated with adenoviruses containing human 15-LO-1 cDNA (Ad-15-LO-1) or beta-galactosidase (Ad-beta-Gal). Ad-15-LO-1-transduction increased the expression of a 75-kDa protein corresponding to 15-LO-1, detected by immunoblotting with an anti-human15-LO-1 antibody, and increased the production of HEETA and THETA from [(14)C]AA. Immunohistochemical studies on Ad-15-LO-1-transduced rabbit aorta showed the presence of 15-LO-1 in endothelial cells. Ad-15-LO-1-treated aortic rings showed enhanced relaxation to AA (max 31.7 +/- 3.2%) compared with Ad-beta-Gal-treated (max 12.7 +/- 3.2%) or control nontreated rings (max 13.1 +/- 1.6%) (P < 0.01). The relaxations in Ad-15-LO-1-treated aorta were blocked by the 15-LO inhibitor cinnamyl-3,4-dihydroxy-a-cyanocinnamate. Overexpression of 15-LO-1 in the rabbit aortic endothelium is sufficient to increase the production of the vasodilatory HEETA and THETA and enhance the relaxations to AA. This confirms the role of HEETA and THETA as endothelium-derived relaxing factors.

Author List

Aggarwal NT, Holmes BB, Cui L, Viita H, Yla-Herttuala S, Campbell WB

Author

William B. Campbell PhD Chair, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-33846980154   14 Citations

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Adenoviridae
Animals
Aorta, Thoracic
Arachidonate 15-Lipoxygenase
Arachidonic Acid
Cells, Cultured
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Endothelial Cells
Genetic Vectors
Hydroxyeicosatetraenoic Acids
Immunohistochemistry
In Vitro Techniques
Lipoxygenase Inhibitors
Molecular Structure
Rabbits
Tandem Mass Spectrometry
Transduction, Genetic
Vasodilation
Vasodilator Agents
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e