F1R1/JAM: Indicator of Human Atherosclerotic Diseases

F1R1/JAM：人类动脉粥样硬化疾病的指标

• 批准号: 6853545
• 负责人: ELIZABETH H KORNECKI
• 金额: $ 15.3万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6853545
• 关键词: atherosclerosis; atherosclerotic plaque; biomarker; cardiovascular disorder diagnosis; cardiovascular disorder risk; cell adhesion molecules; clinical research; coronary disorder; enzyme linked immunosorbent assay; human tissue; immunocytochemistry; northern blottings; platelet aggregation; polymerase chain reaction; protein localization; thrombosis

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.

描述（由申请人提供）：这项研究是为了确定在冠状动脉疾病（CAD）患者中称为F11R/JAM的长期客观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。 血小板对发炎的内皮粘附触发了导致这些病变的血栓形成。 F11受体（F11R）最近确定为对血小板内皮表面血小板粘附至关重要的关键分子。 F11R是一种新型的细胞粘附分子（CAM），是免疫球蛋白（IG）超家族的成员，也是内皮细胞（EC）中发现的鼠类CAM的人类直系同源物，称为连接粘附分子（JAM）。 我们已经确定，测序并克隆了F11R/JAM的人类基因。 在这里，我们将研究以下假设：CAD患者血液中可溶性F11R的水平可以作为动脉粥样硬化的预测指标。 此处提出的项目符合本计划公告要求的所有标准：（a）F11R是一个新颖的凸轮，在血栓形成中起着重要作用。 （b）可用于本研究的大量现有人体组织和流体样本。 （c）这项研究是几所大学基础科学家和血管外科医生之间的合作，（d）该项目代表了基于F11R/JAM的最新基础研究的最新发现，这是首次临床研究，是炎症血栓形成，血小板聚集，粘附，斑块形成和动脉粥样硬化的关键因素。 使用敏感的ELISA程序，该程序由我们开发用于测量人体组织和流体中F11R的试剂的方法，该项目的研究计划旨在实现以下特定目的：（1）确定2050年现有的可溶性F11R水平，现有的，表征的血液样品，从冠状动脉疾病患者和对照组中获得。 （2）测定F11R在血管疾病患者和尸体颈动脉控制供体的动脉粥样硬化斑块中的表达。 预计拟议的研究将提供新的信息，这些信息对于预测冠状动脉和周围动脉疾病的严重程度和进步，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至关重要。