title: Impairment of endothelium-dependent aorta relaxation by phospholipid components of oxidized low-density lipoprotein.
abstract: Oxidized low-density lipoprotein (LDL) is a major component in the pathophysiology of atherosclerosis and plays a role in the changes of vascular reactivity observed in this disease. Herein the authors investigate the potential involvement of platelet-activating factor (PAF)-like phospholipid components of oxidized LDL in rabbit aorta reactivity. Aortic rings were precontracted with noradrenaline (0.5 microM) and relaxation was induced by subsequent stimulation with sequential additions of acetylcholine (1 nM to 3 microM). High-performance liquid chromatography (HPLC) fractions (6- and 7-min) obtained from phospholipids extracted from oxidized LDL inhibited relaxation evoked by acetylcholine, but not the relaxation induced by sodium nitroprusside. This effect was not antagonized either by incubation of the fractions with PAF acetylhydrolase or by incubation of the aortic rings with a PAF receptor antagonist. Authentic PAF or C4-PAF, a PAF mimetic previously found in fractions 6 and 7 did not inhibit acetylcholine-induced relaxation. In contrast, lyso-PAF inhibited acetylcholine, but not sodium nitroprusside-induced relaxation. The authors conclude that phospholipids of oxidized LDL impair vascular reactivity to endothelium-dependent agonists. This effect is not due to oxidatively generated proinflammatory PAF mimetics, but rather to a metabolite of these phospholipids, lysoPAF.
authors.affiliation: Laboratório de Imunofarmacologia Neurocardiovascular, Departamento de Fisiologia e Farmacodinâmica, IOC, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Eunice
authors.initials: E
authors.lastname: Vasques
authors.forename: Andressa L F
authors.initials: AL
authors.lastname: Almeida
authors.forename: Vivian
authors.initials: V
authors.lastname: Noya
authors.forename: Bárbara
authors.initials: B
authors.lastname: D'Alegria
authors.forename: Gopal
authors.initials: G
authors.lastname: Marathe
authors.forename: Thomas M
authors.initials: TM
authors.lastname: McIntyre
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tibiriçá
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Silva
authors.forename: Hugo C
authors.initials: HC
authors.lastname: Castro-Faria-Neto
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010743:Phospholipids / Q000378:metabolism* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D008077:Lipoproteins, LDL; C029271:O-deacetyl platelet activating factor; D010743:Phospholipids; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; C039351:platelet activating factor receptor; D009599:Nitroprusside; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000109:Acetylcholine; D009638:Norepinephrine