PLATELET FUNCTIONAL GENOMICS IN CARDIOVASCULAR DISEASE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。我们假设，血小板粘附性糖蛋白的遗传变异决定了血小板的反应性，从而决定了急性缺血性冠脉综合征的风险。我们的长期目标是通过测量急性冠脉综合征患者的血小板功能并进行血小板基因分型来验证我们的假设。该项目的一个具体目标是确定与对照组相比，是否可以将血小板聚集作为衡量缺血性心脏病患者血小板功能亢进的指标。在急性冠脉综合征出现时和间隔3个月后，进行肾上腺素阈值聚集和使用抗受体诱导结合位点的全血流式细胞术。比较出现时和三个月后进行的血小板功能研究，将评估急性事件发生时血小板功能是否有所不同。具体目标2包括在患者组中进行血小板基因分型，并将这些频率与住院患者的对照组进行比较。具体目标3涉及指标事件与血小板功能和血小板糖蛋白多态的相关性。最后，我们将确定是否可以使用血小板功能和/或血小板糖蛋白基因来预测后续事件。如果基因多态与急性冠脉综合征之间存在相关性，则可以对高危个体进行筛查。未来的研究将旨在评估针对这些人进行积极的预防性干预或抗血小板治疗是否会降低急性冠状动脉事件的风险。在这个项目中获得的信息也可能导致设计用于治疗急性冠脉综合征的新药。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We hypothesize that inherited variations of platelet adhesive glycoproteins determine platelet reactivity and hence, risk for acute ischemic coronary syndrome. Our long-term objective is to validate our hypothesis by measuring platelet function and performing platelet genotyping in patients who present with the acute coronary syndrome. One specific aim of the project involves determining whether platelet aggregation may be used as a measure of platelet hyperfunction in patients with ischemic heart disease when compared to control subjects. Epinephrine threshold aggregation and whole blood flow cytometry using anti-receptor induced binding site binding will be performed at time of presentation with acute coronary syndrome and after 3-month interval. Comparison of platelet function studies performed at presentation and after a three-month interval will assess whether platelet function differs at the time of the acute event. Specific aim 2 involves performing platelet genotyping in the patient group and comparing these frequencies to a control group of hospitalized patients. Specific aim 3 involves correlating index events with platelet function and platelet glycoprotein polymorphism. Finally we will determine whether platelet function and/or platelet glycoprotein genotype can be used to predict subsequent events. If a correlation exists between genetic polymorphisms and the acute coronary syndrome, at risk individuals could be screened for these genetic polymorphisms. Future studies would be designed to evaluate whether targeting these individuals for aggressive preventive interventions or anti-platelet therapy would reduce risk of acute coronary events. The information obtained in this project could also lead to the design of newer medications used for the therapy of the acute coronary syndrome.