MRP-14, Platelets and Atherothrombosis

MRP-14、血小板和动脉粥样硬化血栓形成

• 批准号: 7385675
• 负责人: KEVIN J CROCE
• 金额: $ 13.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385675
• 关键词: Acute; Acute myocardial infarction; Adhesions; Advisory Committees; Affect; Agonist; Angioplasty; Animals; Apolipoprotein E; Arachidonic Acids; Area; Arterial Fatty Streak; Arteries; Atherosclerosis; Biochemistry and Cellular Biology; Biology; Biomedical Research; Blood Platelets; Blood Vessels; Bone Marrow; C-reactive protein; Calcium Signaling; Calgranulin B; Cardiac Catheterization Procedures; Cardiovascular system; Carotid Arteries; Case-Control Studies; Chemotaxis; Chest Pain; Clinical Research; Complex; Coronary; Coronary Arteriosclerosis; Coronary Thrombosis; Coronary artery; Cytoskeletal Modeling; Data; Depth; Development; Disease; Elevation; Environment; Etiology; Event; Family; Future; Gene Expression; Gene Expression Profile; Generations; Genetic Transcription; Hospitals; In Vitro; Individual; Inflammation; Inflammatory Response; Injury; Integrins; Knowledge; Laboratories; Lasers; Lesion; Leukocyte Trafficking; Leukocytes; Ligand Binding; Measures; Medical; Medicine; Megakaryocytes; Mentors; Messenger RNA; Metabolism; Microarray Analysis; Molecular; Mononuclear; Mus; Myelogenous; Myocardial Infarction; Nested Case-Control Study; Odds Ratio; Partner in relationship; Patients; Phagocytes; Phenotype; Physiological reperfusion; Plasma; Play; Principal Investigator; Protein Biosynthesis; Proteins; Reactive Oxygen Species; Recurrence; Regulation; Relative (related person); Reperfusion Therapy; Research; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Rupture; S100A9 gene; Scientist; Signal Transduction; Standards of Weights and Measures; Stroke; Thrombosis; Thromboxanes; Thrombus; Time; Training; Training Programs; Transcript; Validation; Woman; Women' s Health; abstracting; acute coronary syndrome; aged; atherogenesis; atherothrombosis; career; case control; day; design; experience; extracellular; factor C; femoral artery; in vivo; in vivo Model; insight; intravital microscopy; medical schools; member; monocyte; neointima formation; novel; novel strategies; prevent; programs; prospective; research study; response; trend; vascular inflammation

DESCRIPTION (provided by applicant): This revised proposal describes a 5-year training program for career development in academic cardiovascular (CV) medicine. The principal investigator has completed clinical and research training in CV medicine at Brigham and Women's Hospital and will embark on a research program designed to provide additional scientific training required for an independent biomedical research career. This program will provide in-depth knowledge and experience in biochemistry, cellular biology, and in vivo animal studies applied to thrombosis and atherosclerosis. Dr. Peter Libby will mentor the principal investigator's scientific development and Dr. Simon will serve as co-mentor. Dr. Libby is a recognized leader in the field of vascular inflammation and atherosclerosis and has a successful track record in basic and translational vascular biology research. The training experience will be enhanced through collaborative intravital microscopy studies with Dr. Bruce Furie, a leader in thrombosis research. An advisory committee of expert medical scientists (Drs. Daniel Simon, Bruce Furie, Tanya Mayadas-Norton) will provide scientific and career advice. The central hypotheses of this proposal are that MRP-14 modulates platelet and monocyte function and that platelet- and leukocyte-derived MRP-14 affect vascular inflammation and atherogenesis. Preliminary data have identified MRP-14 as a platelet transcript that is elevated in patients on presentation with acute myocardial infarction (Ml) and, in two validation case-control studies, MRP-8/14 predicts risk of Ml. The overall objective of this proposal is to determine the role of MRP-14 in atherothrombotic disease. The specific aims are: 1) to investigate the role of MRP-14 in regulating platelet and monocyte function in vitro; 2) to determine whether MRP-14 modulates arterial thrombosis in vivo; and 3) to examine the role of MRP-14 in vascular inflammation and atherogenesis in vivo. These studies will exploit the use of wild-type and MRP-14-deficient mice. Identification of molecules involved in atherothrombosis will provide potential targets for therapies to prevent heart attack and stroke. The Harvard Medical School/Brigham and Women's Hospital Center of Excellence in Vascular Biology is an exceptional environment that will provide innumerable resources to accelerate the applicant's training for an independent career in academic research. (End of Abstract)

描述（由申请人提供）： 该修订后的提案描述了学术心血管 (CV) 医学职业发展的 5 年培训计划。主要研究者已在布莱根妇女医院完成了心血管医学的临床和研究培训，并将开展一项研究计划，旨在为独立生物医学研究职业提供所需的额外科学培训。该项目将提供生物化学、细胞生物学以及应用于血栓形成和动脉粥样硬化的体内动物研究方面的深入知识和经验。 Peter Libby 博士将指导首席研究员的科学发展，Simon 博士将担任联合导师。 Libby 博士是血管炎症和动脉粥样硬化领域公认的领导者，在基础和转化血管生物学研究方面拥有成功的记录。通过与血栓研究领域的领导者 Bruce Furie 博士合作进行活体显微镜研究，将增强培训经验。由医学专家（Daniel Simon 博士、Bruce Furie、Tanya Mayadas-Norton 博士）组成的咨询委员会将提供科学和职业建议。该提议的中心假设是MRP-14调节血小板和单核细胞功能，并且血小板和白细胞衍生的MRP-14影响血管炎症和动脉粥样硬化形成。初步数据已确定 MRP-14 是一种血小板转录物，在出现急性心肌梗塞 (M1) 的患者中会升高，并且在两项验证病例对照研究中，MRP-8/14 可以预测 M1 的风险。该提案的总体目标是确定 MRP-14 在动脉粥样硬化血栓性疾病中的作用。具体目的是：1）研究MRP-14在体外调节血小板和单核细胞功能的作用； 2)确定MRP-14是否调节体内动脉血栓形成； 3）检查MRP-14在体内血管炎症和动脉粥样硬化形成中的作用。这些研究将利用野生型和 MRP-14 缺陷型小鼠。鉴定参与动脉粥样硬化血栓形成的分子将为预防心脏病和中风的治疗提供潜在靶点。哈佛医学院/布莱根妇女医院血管生物学卓越中心拥有优越的环境，将提供无数资源来加速申请人在学术研究方面独立职业的培训。 （摘要完）