title: Modulation of nitric oxide and 6-keto-prostaglandin F(1alpha) production in bovine aortic endothelial cells by conjugated linoleic acid.
abstract: Conjugated linoleic acid (CLA) refers to a group of polyunsaturated fatty acids that exist as positional (18:2) and stereo (cis/trans) isomers of conjugated dienoic octadecadienoate. Reports consistently indicate that CLA may inhibit both the onset and progression of atherosclerosis, via an as yet unknown mechanism(s). In an effort to identify the putative biochemical effects of CLA on bovine aortic endothelial cells (BAECs), the authors examined both the temporal and dose-dependent effects of a commercial CLA isomeric mixture on the expression and enzymatic function of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-I/II (COX-I/II) in these cells. Initial investigations indicated that CLA mix (0 to 10 microg/mL, 0 to 24 h) failed to regulate either the expression or activity of eNOS in BAECs under basal conditions. Pretreatment of BAECs with CLA mix (10 microg/mL) for either 3 or 24 h, followed by incubation with 5 microM bradykinin (BK) for 3 h, however, increased BK-stimulated nitrite release by 2.4 +/- 0.6- and 3.0 +/- 0.4-fold, respectively, more than control cells (BK-stimulation without CLA pretreatment). Under basal conditions, CLA mix (10 microg/mL, 0 to 24 h) had no significant effect on either COX-I or COX-II expression, genes that could be readily induced in response to hemodynamic stimuli. CLA could, however, significantly attenuate BAEC release of 6-keto-prostaglandin F(1alpha) (6k-PGF(1alpha)), a stable breakdown product of prostaglandin I2 (PGI2) within the cyclooxygenase pathway, in a dose- and time-dependent manner. In conclusion, therefore, the results suggest that CLA may potentiate agonist-stimulated eNOS activation whilst attenuating COX-dependent PGI2 synthesis in BAECs. This ability to increase agonist-stimulated nitric oxide (NO) levels, whilst reducing production of inflammatory mediators within vascular ECs, supports a putative atheroprotective role for CLA and provides an important biochemical insight into its purported ability to modulate endothelium-mediated vascular homeostasis.
authors.affiliation: Vascular Health Research Centre, School of Biotechnology, Faculty of Science and Health, Dublin City University, Glasnevin, ublin, Ireland.
authors.forename: Paul
authors.initials: P
authors.lastname: Coen
authors.forename: Philip
authors.initials: P
authors.lastname: Cummins
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Birney
authors.forename: Rosaleen
authors.initials: R
authors.lastname: Devery
authors.forename: Paul
authors.initials: P
authors.lastname: Cahill
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D007527:Isoenzymes; D044243:Linoleic Acids, Conjugated; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001920:Bradykinin