PLATELET FUNCTIONAL GENOMICS IN CARDIOVASCULAR DISEASE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们假设血小板粘附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状动脉综合征的风险。我们的长期目标是通过测量急性冠状动脉综合征患者的血小板功能和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的是确定血小板聚集是否可以作为缺血性心脏病患者血小板功能亢进的测量指标，并与对照组进行比较。肾上腺素阈值聚集和使用抗受体诱导结合位点结合的全血流式细胞术将在急性冠状动脉综合征出现时和间隔3个月后进行。在发病时和三个月间隔后进行血小板功能研究的比较将评估急性事件时血小板功能是否不同。具体目标2包括对患者组进行血小板基因分型，并将这些频率与住院患者对照组进行比较。具体目标3涉及血小板功能和血小板糖蛋白多态性相关指标事件。最后，我们将确定血小板功能和/或血小板糖蛋白基因型是否可用于预测后续事件。如果基因多态性与急性冠状动脉综合征之间存在相关性，则可以对这些基因多态性进行高危个体筛查。未来的研究将旨在评估针对这些个体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用于治疗急性冠脉综合征的新药物的设计。

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.