title: Acyl chain-dependent effect of lysophosphatidylcholine on endothelium-dependent vasorelaxation.
abstract: Previously we identified palmitoyl-, oleoyl-, linoleoyl-, and arachidonoyl-lysophosphatidylcholine (LPC 16:0, 18:1, 18:2 and 20:4) as the most prominent LPC species generated by endothelial lipase (EL). In the present study, we examined the impact of those LPC on acetylcholine (ACh)- induced vascular relaxation. All tested LPC attenuated ACh-induced relaxation, measured ex vivo, using mouse aortic rings and wire myography. The rank order of potency was as follows: 18:2>20:4>16:0>18:1. The attenuating effect of LPC 16:0 on relaxation was augmented by indomethacin-mediated cyclooxygenase (COX)-inhibition and CAY10441, a prostacyclin (PGI2)- receptor (IP) antagonist. Relaxation attenuated by LPC 20:4 and 18:2 was improved by indomethacin and SQ29548, a thromboxane A2 (TXA2)- receptor antagonist. The effect of LPC 20:4 could also be improved by TXA2- and PGI2-synthase inhibitors. As determined by EIA assays, the tested LPC promoted secretion of PGI2, TXA2, PGF2α, and PGE2, however, with markedly different potencies. LPC 16:0 was the most potent inducer of superoxide anion production by mouse aortic rings, followed by LPC 18:2, 20:4 and 18:1, respectively. The strong antioxidant tempol recovered relaxation impairment caused by LPC 18:2, 18:1 and 20:4, but not by LPC 16:0. The tested LPC attenuate ACh-induced relaxation through induction of proconstricting prostanoids and superoxide anions. The potency of attenuating relaxation and the relative contribution of underlying mechanisms are strongly related to LPC acyl-chain length and degree of saturation.
authors.affiliation: Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria.
authors.forename: Shailaja P
authors.initials: SP
authors.lastname: Rao
authors.forename: Monika
authors.initials: M
authors.lastname: Riederer
authors.forename: Margarete
authors.initials: M
authors.lastname: Lechleitner
authors.forename: Martin
authors.initials: M
authors.lastname: Hermansson
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Graier
authors.forename: Saša
authors.initials: S
authors.lastname: Frank
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000378:metabolism; D013928:Thromboxane A2 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D008244:Lysophosphatidylcholines; D011453:Prostaglandins; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine