F1R1/JAM: Indicator of Human Atherosclerotic Diseases

描述（由申请人提供）：本研究的目的是确定冠状动脉疾病（CAD）患者中称为F11R/JAM的长期目标蛋白水平的测量可以作为动脉粥样硬化病变形成的重要指标。血小板粘附在发炎的内皮上触发血栓形成，导致这些病变。最近发现的血小板粘附到血栓形成的内皮表面的关键分子是F11受体（F11R）。F11R是一种新的细胞粘附分子（CAM），是免疫球蛋白（Ig）超家族的成员，是内皮细胞（EC）中发现的小鼠CAM的人类同源物，称为连接粘附分子（JAM）。我们已经鉴定、测序和克隆了人类F11R/JAM基因。在这里，我们将检验CAD患者血液中可溶性F11R水平可以作为动脉粥样硬化预测指标的假设。本项目符合本项目公告要求的所有标准：(a) F11R是一种新型CAM，在血栓形成中起重要作用。(b)现有的大量人体组织和体液样本可用于这项研究。(c)本研究是几所大学的基础科学家和血管外科医生的合作，(d)本项目是基于F11R/JAM作为炎症血栓形成、血小板聚集、粘连、斑块形成和动脉粥样硬化的关键因素的最新前沿基础研究成果的第一个临床研究。使用由我们开发的用于测量人体组织和液体中F11R的试剂组成的敏感ELISA程序，本项目的研究计划旨在实现以下具体目标：(1)测定2050年从冠心病患者和对照组获得的现有特征血液样本中可溶性F11R的水平。(2)检测F11R在血管病患者和颈动脉对照供体动脉粥样硬化斑块中的表达。拟议的研究预计将提供新的信息，在预测冠状动脉和外周动脉疾病的严重程度和进展，开发新的治疗药物，以及预防和治疗血栓和动脉粥样硬化方面具有至关重要的意义。

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.