F1R1/JAM: Indicator of Human Atherosclerotic Diseases

Suny Downstate Medical Center, Brooklyn NY

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Abstract

DESCRIPTION (provided by applicant): The of this research is to establish that the measurement of levels of the long-term objective protein termed F11R/JAM in patients with Coronary artery disease (CAD) can serve as a significant indicator of the formation of atherosclerotic lesions. Platelet adhesion to the inflamed endothelium triggers the formation of thrombi leading to these lesions. A key molecule identified recently as critical for platelet adhesion to a thrombogenic endothelial surface is the F11 receptor (F11R). F11R is a novel cell adhesion molecule (CAM), a member of the immunoglobulin (Ig) superfamily, and a human ortholog of a murine CAM found in endothelial cells (EC), termed Junctional Adhesion Molecule (JAM). We have identified, sequenced, and cloned the human gene for F11R/JAM. Here we shall examine the hypothesis that the level of soluble F11R in the blood of CAD patients can serve as a predictive indicator of atherosclerosis. The project proposed here fulfills all of the criteria requested by this Program Announcement: (a) F11R is a novel CAM with an important role in thrombus formation. (b) A large number of existing samples of human tissue and fluids are available for this research. (c) This study is a collaboration among basic scientists and vascular surgeons at several universities, and (d) This project represents the first clinical investigation based on recent findings of cutting-edge basic research on F11R/JAM as a critical factor in inflammatory thrombosis, platelet aggregation, adhesion, plaque formation and atherosclerosis. Using a sensitive ELISA procedure consisting of reagents that we have developed for measuring F11R in human tissues and fluids, the Research Plan of this project is designed to achieve the following Specific Aims: (1) Determination of levels of soluble F11R in 2050 existing, characterized blood samples obtained from coronary artery disease patients and controls. (2) Determination of the expression of F11R in atherosclerotic plaques of vascular disease patients and cadaveric carotid artery control donors. The proposed studies are expected to provide novel information that would be of crucial importance in the prediction of the severity and progress of coronary and peripheral artery disease, for the development of new therapeutic drugs, and for the prevention and treatment of thrombosis and atherosclerosis.