F1R1/JAM: Indicator of Human Atherosclerotic Diseases

描述（由申请方提供）：本研究旨在确定冠状动脉疾病（CAD）患者中称为F11 R/JAM的长期目标蛋白水平的测量可作为动脉粥样硬化病变形成的重要指标。 血小板粘附到发炎的内皮触发血栓形成，导致这些病变。 最近发现的一个关键分子是F11受体（F11 R），它对血小板粘附于血栓形成的内皮表面至关重要。 F11 R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，并且是在内皮细胞（EC）中发现的鼠CAM的人直系同源物，称为连接粘附分子（JAM）。 我们已经确定，测序和克隆的F11 R/JAM的人类基因。 在这里，我们将检查的假设，即可溶性F11 R在CAD患者的血液中的水平可以作为动脉粥样硬化的预测指标。 此处提议的项目满足本计划公告要求的所有标准：（a）F11 R是一种新型CAM，在血栓形成中发挥重要作用。 (b)大量现有的人体组织和体液样本可用于这项研究。 (c)这项研究是几所大学的基础科学家和血管外科医生之间的合作，以及（d）该项目是基于F11 R/JAM作为炎性血栓形成、血小板聚集、粘附、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结果的第一项临床研究。 本项目的研究计划使用我们开发的用于测量人体组织和体液中F11 R的试剂组成的灵敏ELISA方法，旨在实现以下特定目标：（1）测定从冠状动脉疾病患者和对照组获得的2050份现有的、表征的血液样本中可溶性F11 R的水平。 (2)血管疾病患者和尸体颈动脉对照供体动脉粥样硬化斑块中F11 R表达的测定。 这些研究有望为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形成和动脉粥样硬化提供至关重要的新信息。

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.