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Interactive Signaling Modules in Vascular Inflammation

血管炎症中的交互式信号模块

基本信息

批准号：
8266925
负责人：
LINDA H SHAPIRO
金额：
$ 8.62万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8266925
关键词：
Accounting Address Adhesions Adhesives Adult Affect Age Animal Model Annexins Apolipoprotein E Apoptosis Apoptotic Area Arterial Fatty Streak Atherosclerosis Attention Attenuated Autoimmune Process Biochemical Biochemistry Bioinformatics Biological Biological Assay Biological Factors Biological Phenomena Biological Process Biological Response Modifiers Biology Blood Vessels CCL2 gene Caenorhabditis elegans Cardiovascular Diseases Caspase Caspase Inhibitor Cause of Death Caveolae Cell Adhesion Cell Communication Cell Culture Techniques Cell Surface Proteins Cell Survival Cell membrane Cell physiology Cell surface Cell-Cell Adhesion Cells Cellular biology Cessation of life Chemotactic Factors Chemotaxis Cholesterol Chronic Clear Cell Coagulation Process Collaborations Collagen Complex Confocal Microscopy Connecticut Consensus Consultations Core Facility Coupled Data Databases Dengue Hemorrhagic Fever Derivation procedure Development Developmental Biology Diabetes Mellitus Diagnostic Discipline Disease Disease Progression Dissection Economic Burden Elderly Elements Endothelial Cells Endothelium Environment Essential Hypertension Event Evolution Excision Experimental Autoimmune Encephalomyelitis Faculty Fluorescence Microscopy Foam Cells Fostering Functional disorder Funding Future G Protein-Coupled Receptor Genes GTP-Binding Proteins Generations Genes Genetic Glutamate Carboxypeptidase II Goals Guanine Nucleotide Exchange Factors Head Health Health Expenditures Heart Diseases Hematopoietic Hematoxylin Histology Home environment Homing Housing Human Hypoxia Image Image Analysis Imaging technology Immigration Immune Immunohistochemistry Immunologics In Situ Hybridization In Vitro Incidence Inflammation Inflammation Process Inflammatory Instruction Integrins Interleukin-1 Investigation Ischemia Knockout Mice Knowledge Lead Lesion Leukocytes Life Ligands Lipids Lupus Lysophospholipids Mass Spectrum Analysis Mediating Mediator of activation protein Membrane Membrane Lipids Membrane Microdomains Metabolism Microscopy Modeling Molecular Morbidity - disease rate Mus Myelogenous Myeloid Cells Myocardial Infarction National Center for Research Resources Natural Killer Cells Neoplasm Metastasis Neuropathy Nucleic Acid Probes Obstruction Organ Organism PTEN gene Participant Pathogenesis Pathologic Pathologist Pathology Pathway interactions Penetration Peptide Hydrolases Phagocytosis Pharmacologic Substance Phase III Clinical Trials Phenotype Physiological Physiology Plant Roots Polysaccharides Prevention Procedures Process Program Research Project Grants Protein Isoforms Protein Kinase C Proteins Proteomics Publishing Quality Control Reagent Receptor Signaling Recording of previous events Regulation Research Research Personnel Resolution Resources Retinal Diseases Rheumatoid Arthritis Risk Factors Role Rupture Saffron Sampling Sepsis Services Sialic Acids Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Protein Site Smooth Muscle Myocytes Specimen Sphingolipids Sphingomyelins Sphingosine-1-Phosphate Receptor Staining method Stains Stroke Subcellular structure System T-Lymphocyte Techniques Technology Therapeutic Thick Thrombosis Time Tissues Training Training Programs Translations Trees Trustees Tyrosine Phosphorylation United States United States National Institutes of Health Universities Vascular Endothelial Cell Vascular System Woman Work alanine aminopeptidase angiogenesis atherogenesis autoimmune vasculitis base blood glucose regulation blood lipid body system cell behavior cell injury cell motility cell type cellular imaging chemokine clinically relevant cytokine design fluorescence imaging in vivo inhibitor/antagonist insight instrumentation interdisciplinary approach interest investigator training macrophage mast cell meetings member migration molecular pathology monocyte mortality mouse model multidisciplinary neutrophil novel novel strategies novel therapeutics oncology operation planetary Atmosphere plaque lesion premature programs protein activation receptor reconstruction research study sex skills sphingosine 1-phosphate therapeutic development tool trafficking transplant associated vasculopathy two-photon uptake vascular inflammation

项目摘要

The competitive renewal of the program project application "Interactive signaling modules in vascular inflammation" is focused on the process of inflammatory changes in the vessel wall that lead to atherosclerosis. The program brings together seven independent investigators interested in the vascular biology. The theme of the program is to define molecular mechanisms important for pathologic inflammatory events with a focus on myeloid cells. The central hypothesis is that interactions between distinct signal transduction modules influence fundamental cellular processes such as cell-cell interaction, cell migration, inflammation, death and engulfment of apoptotic cells, ultimately altering the pathogenesis and progression of atherosclerosis. Each project in the program focuses on a unique aspect of the theme to advance our understanding of inflammatory vascular phenotypes. Project 1 (Hla) proposes to investigate the role of sphingosine 1-phosphate on macrophage inflammasome function and atherogenesis. This project shares several common interests with Project 2 (Wu), which is focused on PLCB regulation of macrophage apoptosis and atherogenesis. Project 3 (Han) focuses on the process of cell-cell recognition process by which apoptotic cells are cleared from the vascular wall. Thus, this project has common interests as projects 2 and 4. Project 4 (Shapiro) focuses on the novel role of the cell-surface molecule CD13 in the adhesion of myeloid cells to vascular endothelial cells, and explores this mechanism in vascular pathology. All the projects utilize molecular, biochemical, cell biological and in vivo mouse models. Thus three cores, administrative, fluorescence imaging and vascular histology and atherosclerosis are proposed to support the projects with state-of-the-art technology. All the projects and cores interact and mutually reinforce each other to achieve the goals of the program in a synergistic manner. Coupled with strong institutional support to the Center for Vascular Biology, it is anticipated that significant new insights on vascular inflammation and atherosclerosis will be forthcoming from this renewal program project application. RELEVANCE (See instructions): Inflammation in the vessel wall is important in atherosclerosis, which leads to heart attacks. Blood monocytes enter the vessel wall, differentiate into macrophages and sustain inflammation. This project will focus on new mechanisms of monocyte entry, macrophage inflammatory mechanisms, macrophage survival and engulfment of dead or apoptotic cells. These collaborative studies should lead to better understanding of atherosclerosis and provide potential new therapeutic directions to control atherosclerosis.

项目申请“血管炎症中的交互式信号模块”的竞争性更新重点关注导致动脉粥样硬化的血管壁炎症变化过程。该计划汇集了七名对血管生物学感兴趣的独立研究人员。该计划的主题是定义对病理炎症事件重要的分子机制，重点关注骨髓细胞。中心假设是不同信号转导模块之间的相互作用影响基本的细胞过程，例如细胞间相互作用、细胞迁移、炎症、死亡和凋亡细胞的吞噬，最终改变动脉粥样硬化的发病机制和进展。该计划中的每个项目都侧重于主题的独特方面，以增进我们对炎症血管表型的理解。项目 1 (Hla) 提议研究 1-磷酸鞘氨醇对巨噬细胞炎症小体功能和动脉粥样硬化形成的作用。该项目与项目 2 (Wu) 有几个共同的兴趣，项目 2 的重点是 PLCB 对巨噬细胞凋亡和动脉粥样硬化的调节。项目3（Han）专注于细胞间识别过程，通过该过程将凋亡细胞从血管壁上清除。因此，该项目与项目2和项目4具有共同的兴趣。项目4（Shapiro）重点关注细胞表面分子CD13在骨髓细胞与血管内皮细胞粘附中的新作用，并探索血管病理学中的这一机制。所有项目均利用分子、生化、细胞生物学和体内小鼠模型。因此，提出了三个核心：管理、荧光成像、血管组织学和动脉粥样硬化，以支持最先进技术的项目。所有项目和核心相互作用，相互促进，以协同的方式实现该计划的目标。加上对血管生物学中心的强有力的机构支持，预计这一更新计划项目申请将带来关于血管炎症和动脉粥样硬化的重要新见解。相关性（参见说明）：血管壁炎症在动脉粥样硬化中很重要，从而导致心脏病发作。血液单核细胞进入血管壁，分化为巨噬细胞并维持炎症。该项目将重点研究单核细胞进入的新机制、巨噬细胞炎症机制、巨噬细胞存活以及吞噬死亡或凋亡细胞。这些合作研究应该有助于更好地了解动脉粥样硬化，并为控制动脉粥样硬化提供潜在的新治疗方向。