Platelet Functional Genomics in Cardiovascular Disease

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): We hypothesize that inherited variations of platelet adhesive glycoproteins determine platelet reactivity and hence, risk for acute ischemic coronary syndrome. The long-term objective of our project 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 this project involves determining whether platelet aggregation may be used as a measure of platelet hyperfunction in patients with ischemic heart disease. Epinephrine threshold aggregation and whole blood flow cytometry using anti-receptor induced binding site binding on presentation and at a 3-month interval are two methods utilized to determine this specific aim. A second specific aim involves performing platelet genotyping in the patient group and comparing these frequencies to a control group of hospitalized patients. A third specific aim involves correlating index events with platelet function and platelet glycoprotein polymorphism. Finally a determination of whether platelet function and/or platelet glycoprotein genotype can be used to predict subsequent events will be determined by statistical analysis. Follow-up of patients after a three-month interval from presentation is done to assess any difference in platelet function when compared to acute event presentation. If a correlation exists between genetic polymorphisms and the acute coronary syndrome, then several people can be screened and interventions such as smoking cessation, aggressive lipid management and other preventive medical therapies may be instituted for patients who are at greatest risk. The information gleaned from this project can also lead to new ideas for the design of newer medications used for the therapy of the acute coronary syndrome. The candidate?s career goal includes the refinement of basic laboratory skills pertaining to various platelet assays, development of a better understanding of platelet physiology, eventual establishment of an independent platelet laboratory, and advancement to the level of clinical leader in the field of platelet physiology as it applies to the acute coronary syndrome. By following these career goals, the candidate will eventually be able to ask pertinent questions applicable to the acute coronary syndrome and platelet function and become an independent clinical investigator.