title: Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease.
abstract: Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator of numerous inflammatory and thrombotic responses. The purpose of this study was to determine if PAF synthesis is elevated in damaged coronary arteries after a sustained period of cyclic flow variation (CFV), a phenomenon caused by alternating periods of thrombosis and reperfusion at sites of endothelial injury. Cyclic flow was established and maintained in the left anterior descending coronary arteries (LADs) of 10 dogs. After 8 hours of CFV, the section of damaged LAD containing the thrombus and control sections of the circumflex artery, carotid artery, and saphenous vein was excised, and the total lipids were extracted. The PAF was then purified by silica column chromatography and high-performance liquid chromatography and assayed by both a rabbit platelet bioassay and a PAF radioimmunoassay. With the platelet bioassay, PAF levels of 8.9 +/- 4.0 (range, 4.8 to 15.5) pg/mg wet wt were found in the damaged LADs from the 10 dogs. This PAF bioactivity was completely inhibited by a PAF receptor antagonist. When the radioimmunoassay was used, slightly higher PAF levels of 16.3 +/- 12.9 (range, 4.5 to 41.8) pg/mg wet wt were observed in the LADs. Overall, these PAF levels were 3- to 64-fold higher than in the control vessels when either assay method was used. Although increases in PAF were observed in the damaged LADs, measurements of PAF in blood samples taken from the LAD and the aorta (control) failed to demonstrate any site-specific increase of PAF in the blood. In related experiments, PAF was also measured in 23 endarterectomy samples taken from the coronary arteries of 16 patients with severe atherosclerosis. The PAF levels in these samples were highly variable (2.9 +/- 2.2 [range, 0.3 to 8.5] pg/mg wet wt) and showed no correlation with tissue mass, suggesting that PAF is affected by factors other than the simple presence of atherosclerotic tissue in the vessel. These findings provide direct evidence that PAF is synthesized locally at the site of endothelial injury during thrombosis and that PAF accumulates in the atherosclerotic plaque of some patients with advanced coronary artery disease.
authors.affiliation: Division of Cardiology, University of Texas Health Science Center, Houston 77030, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Mueller
authors.forename: C A
authors.initials: CA
authors.lastname: Haught
authors.forename: J M
authors.initials: JM
authors.lastname: McNatt
authors.forename: K
authors.initials: K
authors.lastname: Cui
authors.forename: S J
authors.initials: SJ
authors.lastname: Gaskell
authors.forename: D A
authors.initials: DA
authors.lastname: Johnston
authors.forename: J T
authors.initials: JT
authors.lastname: Willerson
mesh_terms: D000818:Animals; D001681:Biological Assay; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D003328:Coronary Thrombosis / Q000378:metabolism* / Q000503:physiopathology; D003331:Coronary Vessels / Q000737:chemistry* / Q000378:metabolism; D004285:Dogs; D004691:Endarterectomy; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D010972:Platelet Activating Factor / Q000032:analysis* / Q000096:biosynthesis / Q000378:metabolism; D011817:Rabbits; D011863:Radioimmunoassay; D013997:Time Factors
chemical_list: D010972:Platelet Activating Factor