Binding of apoE-rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation.
Binding of apoE-rich high density lipoprotein particles by saturable sites on human blood platelets inhibits agonist-induced platelet aggregation.
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发表时间：
1989-06
影响因子：
6.5
通讯作者：
K. Desai;Bruckdorfer Kr;R. Hutton;J. Owen
中科院分区：
文献类型：
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作者：
K. Desai;Bruckdorfer Kr;R. Hutton;J. Owen
据报道，高密度脂蛋白(高密度脂蛋白，d 1.063-1.21g/ml)可刺激、不影响或抑制激动剂诱导的血小板聚集。我们假设，这些相互矛盾的报告可能是由个别高密度脂蛋白亚类对血小板聚集性的相反影响来解释的。生理浓度的HDL3对ADP诱导的洗涤血小板悬浮液的聚集几乎没有影响，尽管较高的浓度有刺激作用。正常浓度的HDL2(0.2-0.4 mg蛋白质/毫升)抑制聚集；肝素-琼脂糖层析进一步分离鉴定富含载脂蛋白E的颗粒，称为高密度脂蛋白-E，是主要的抗聚集亚类。洗涤过的血小板与放射性碘标记的高密度脂蛋白-E结合到一类统一的饱和部位；每个血小板的数目为4,200个，Kd值为7.9×10(-7)M。高密度脂蛋白-E与血小板的结合及其抗聚集作用，显示出类似的快速，均发生在生理浓度范围内。此外，这两个过程与二价离子的存在无关，并受到高密度脂蛋白-E载脂蛋白成分的化学修饰的影响。我们的结论是，高密度脂蛋白-E颗粒占据细胞表面受体会削弱血小板对外源性激动剂的反应性，并且在存在完整高密度脂蛋白的情况下，血小板的聚集性可能反映了特定样本中个别亚类的相对浓度。
High density lipoproteins (HDL, d 1.063-1.21 g/ml) are reported to stimulate, to have no effect on, or to inhibit agonist-induced platelet aggregation. We have hypothesized that these conflicting reports might be explained by opposing effects of individual HDL subclasses on platelet aggregability. Physiologic concentrations of HDL3 had little effect on ADP-induced aggregation of washed platelet suspensions, although higher levels were stimulatory. Normal concentrations of HDL2 (0.2-0.4 mg of protein/ml) inhibited aggregation; further fractionation by heparin-Sepharose chromatography identified the particles rich in apolipoprotein E, termed HDL-E, as the major anti-aggregatory subclass. Washed platelets bound radioiodinated HDL-E to a uniform class of saturable sites; they numbered 4,200 per platelet and the KD was 7.9 x 10(-7) M. Binding of HDL-E by platelets, and its anti-aggregatory action, showed a similar rapidity and both occurred within the physiologic concentration range. Moreover, the two processes were independent of the presence of divalent ions and were impaired by chemical modification of the apolipoprotein constituents of HDL-E. We conclude that occupation of cell-surface receptors by HDL-E particles impairs platelet responsiveness to exogenous agonists and that platelet aggregability in the presence of whole HDL may reflect the relative concentrations of the individual subclasses in the particular sample.