Genetic and Cellular Determinants of Arterial Thrombosis

Cleveland Clinic Lerner Com-Cwru, Cleveland OH

Investigators

Linked publications & trials

Abstract

Arterial thrombosis as the proximate cause of myocardial infarction, stroke, and limb gangrene remains the[unreadable] most important cause of mortality and morbidity in the USA. Blood platelets play a critical role in initiating[unreadable] arterial thrombi. The overall goal of this SCCOR is to discover genetic and cellular determinants of altered[unreadable] platelet function in systemic inflammatory states, such as atherosclerosis and diabetes. We have assembled[unreadable] a multidisciplinary team of clinical, basic and translational scientists and developed a Center with 6 scientific[unreadable] projects and 6 cores. Project 1 will use in vitro assays, in vivo mouse genetic models, and human genetic[unreadable] studies to examine the novel hypothesis that platelet glycoprotein CD36 mediates platelet hyper-reactivity[unreadable] associated with atherosclerosis, diabetes, and inflammation. Project 2 will explore a critically important[unreadable] clinical problem, platelet resistance to pharmacologic interventions, and will utilize a targeted human genetic[unreadable] approach coupled to sophisticated in vitro assessment of platelet function. Project 3 will explore the[unreadable] mechanistic role of platelet activating factor (PAF) in mediating the interface between inflammation and[unreadable] thrombosis. Project 4 will study a clinical population of patients undergoing endovascular carotid stenting as[unreadable] a model of the vulnerable plaque, focusing on developing novel imaging tools and biomarkers. Project 5 will[unreadable] study leukocyte-platelet interactions, focusing on the role of the Mac-1 integrin in regulating thrombosis.[unreadable] Project 6 will study patients with anti-phospholipid syndrome, an autoimmune disease that is an important[unreadable] cause of thrombosis, especially in young women, to characterize determinants of thrombotic risk. Core A will[unreadable] provide administrative support, Core B biostatistics support and Core C an infrastructure to support the[unreadable] clinical research components of all 6 projects. Core D will provide high throughput human genotyping[unreadable] services and Core E flow cytometry and mass spectrometry services. Core F will provide a curriculum and[unreadable] career development support for physicians training in clinical thrombosis research in SCCOR laboratories.