Gross P L, Rand M L, Barrow D V, Packham M A
Department of Biochemistry, University of Toronto, Ontario, Canada.
Arterioscler Thromb. 1991 May-Jun;11(3):610-6. doi: 10.1161/01.atv.11.3.610.
The characteristics of platelets from seven 5-7-month-old homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits (plasma cholesterol, 13.9 +/- 1.7 mM, mean +/- SEM) were compared with those of platelets from normocholesterolemic age/weight- and sex-matched control rabbits (plasma cholesterol, 2.2 +/- 0.3 mM). Whole-blood platelet count and platelet size and protein content were not different in the two groups of rabbits, and the platelets from the WHHL rabbits were not enriched in cholesterol as indicated by identical mean cholesterol:phospholipid molar ratios (C/P). Responses of washed platelets stimulated with various agonists were studied to determine the effects of the genetically determined hypercholesterolemia on the various pathways of platelet aggregation in the absence of plasma components. In platelets from WHHL rabbits compared with controls, aggregation induced by ADP (0.5-5 microM) did not differ; collagen-induced (0.25-1.5 micrograms/ml) responses (aggregation, secretion of carbon-14-labeled serotonin from the amine storage granules of prelabeled platelets, and thromboxane A2 [TxA2] formation) were significantly less extensive; with aspirin-treated platelets, aggregation and secretion of granule contents induced by the TxA2 mimetic U46619 (0.25-1 microM) were significantly less extensive; and thrombin-induced (0.005-0.1 unit/ml) responses of untreated platelets (aggregation, secretion of granule contents, and TxA2 formation) or aspirin-treated platelets (aggregation and secretion of granule contents) did not differ. These observations are in direct contrast with previous studies of platelets from rabbits with diet-induced hypercholesterolemia, in which responses to TxA2 and thrombin were enhanced. Platelets from WHHL rabbits are hyposensitive to aggregation induced by TxA2.
将7只5 - 7月龄的纯合渡边遗传性高脂血症（WHHL）兔（血浆胆固醇，13.9±1.7 mM，均值±标准误）的血小板特征与年龄、体重和性别匹配的正常胆固醇水平对照兔（血浆胆固醇，2.2±0.3 mM）的血小板特征进行比较。两组兔的全血血小板计数、血小板大小和蛋白质含量无差异，且WHHL兔的血小板胆固醇含量未增加，这可通过相同的平均胆固醇：磷脂摩尔比（C/P）得以证明。研究了用各种激动剂刺激洗涤后的血小板的反应，以确定遗传性高胆固醇血症在无血浆成分情况下对血小板聚集的各种途径的影响。与对照组相比，WHHL兔血小板对ADP（0.5 - 5 microM）诱导的聚集无差异；胶原诱导（0.25 - 1.5微克/毫升）的反应（聚集、预标记血小板胺储存颗粒中碳 - 14标记的5 - 羟色胺分泌以及血栓素A2 [TxA2]形成）明显较弱；对于用阿司匹林处理的血小板，TxA2模拟物U46619（0.25 - 1 microM）诱导的聚集和颗粒内容物分泌明显较弱；未处理血小板（聚集、颗粒内容物分泌和TxA2形成）或用阿司匹林处理的血小板（聚集和颗粒内容物分泌）对凝血酶诱导（0.005 - 0.1单位/毫升）的反应无差异。这些观察结果与先前对饮食诱导的高胆固醇血症兔血小板的研究形成直接对比，在先前研究中，对TxA2和凝血酶的反应增强。WHHL兔的血小板对TxA2诱导的聚集反应不敏感。
