血小板GP IIIa Pl(A) 多态表现出对激动剂的不同敏感性
A D Michelson1, M I Furman, P Goldschmidt-Clermont
1Departments of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Circulation
|March 7, 2000
概括
血小板中的Pl(A2) 基因变异增加了它们的活性和激活. 血小板功能中的这种遗传差异可能解释了对冠状动脉事件的遗传倾向.
科学领域:
- 心血管遗传学 心血管遗传学
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 遗传性倾向和血小板过敏反应与缺血性冠状动脉事件有关.
- 血小板功能的遗传差异背后的机制尚不清楚.
- 糖蛋白IIIa (GP IIIa) 的Pl(A2) 多态性与冠状动脉综合征有关,促使人们对其在血小板高反应性中的作用进行调查.
研究的目的:
- 描述具有Pl(A) (HPA-1) 多态性的血小板的功能参数.
- 调查GP IIIa中Leu (Pl(A1) 替换为Pro (Pl(A2)) 对血小板激活和功能的影响.
- 确定Pl(A2) 变异是否有助于血小板过敏反应,并影响对抗血小板药物的反应.
主要方法:
- 研究了56名健康的捐赠者,他们的基因型为Pl(A) 多态 (Pl(A1,A1),Pl(A1,A2),Pl(A2,A2).
- 评估表面表达的P-选择素,GP IIb/IIIa结合的纤维素原,以及在对腺二酸盐 (ADP) 的反应中激活的GP IIb/IIIa.
- 评估了对阿司匹林和abciximab的血小板聚合敏感性.
主要成果:
- 在低剂量ADP刺激后,pl(A2) 阳性血小板表现出基因剂量效应,与pl(A1,A1) 血小板相比,P-选择素,纤维素结合和GP IIb/IIIa激活显著更大.
- 在Pl(A2,A2) 血小板中,ADP刺激的GP IIb/IIIa表达显著更高.
- 对于PlA等位基 (PlA1,A2) 异构的血小板对阿司匹林和abciximab抑制聚合的敏感性增加.
结论:
- Pl(A2) 阳性血小板显示激活值较低.
- 异合体Pl(A) 血小板对常见的抗血小板药物表现出高度敏感.
- 这些体外发现表明,对于理解体内血栓状况和个性化抗血小板治疗的潜在相关性.
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