Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease.
Measurement of platelet-activating factor in a canine model of coronary thrombosis and in endarterectomy samples from patients with advanced coronary artery disease.
复制标题
犬冠状动脉血栓形成模型和晚期冠状动脉疾病患者动脉内膜切除术样本中血小板活化因子的测量。
DOI：
10.1161/01.res.77.1.54
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发表时间：
1995
影响因子：
20.1
通讯作者：
Willerson,JT
中科院分区：
文献类型：
--
作者：
Mueller,HW;Haught,CA;McNatt,JM;Cui,K;Gaskell,SJ;Johnston,DA;Willerson,JT
血小板活化因子(PAF，1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine))是许多炎症和血栓反应的有效磷脂介质。本研究的目的是确定在血管内皮损伤部位血栓形成和再灌注期交替出现的循环血流变异(CFV)后，受损冠状动脉中PAF的合成是否增加。在10只犬的左冠状动脉前降支(LAD)建立并维持循环血流。CFV治疗8h后，取左前降支损伤段的回旋动脉、颈动脉、大隐静脉血栓段和对照段，提取总脂质。用硅胶柱层析和高效液相色谱分离纯化PAF，并用兔血小板生物测定法和PAF放射免疫测定法进行测定。经血小板生物活性测定，10只犬受损LAD的PAF水平为8.9±4.0(4.8~15.5)pg/mg湿重。这种PAF生物活性可被PAF受体拮抗剂完全抑制。用放射免疫法测定时，LAD组PAF水平略高，为16.3±12.9(4.5~41.8)pg/mg湿重。总体而言，当使用任何一种检测方法时，这些PAF水平都比对照血管高3到倍。尽管在受损的LAD中观察到PAF的增加，但从LAD和主动脉(对照)采集的血液样本中的PAF的测量未能显示出血液中PAF的任何部位特异性增加。在相关实验中，还对16例重度动脉粥样硬化患者的23例冠状动脉内膜剥脱术标本进行了PAF测定。这些样本中的PAF水平变化很大(2.9±2.2[范围，0.3~8.5]pg/mg湿重)，与组织质量无关，提示PAF受血管内单纯存在动脉粥样硬化组织以外的其他因素的影响。这些发现提供了PAF在血栓形成过程中在内皮损伤部位局部合成，以及PAF在一些晚期冠状动脉疾病患者的动脉粥样硬化斑块中积聚的直接证据。
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.