PLATELET FUNCTIONAL GENOMICS IN CARDIOVASCULAR DISEASE

这个子项目是众多研究子项目之一

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.