权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Immune Cell Interactions in Atherosclerosis

动脉粥样硬化中的免疫细胞相互作用

基本信息

批准号：
9280661
负责人：
Catherine C Hedrick
金额：
$ 267.56万
依托单位：
LA JOLLA INSTITUTE FOR IMMUNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9280661
关键词：
Acute Age Antibodies Antigens Apolipoproteins B Arteries Atherosclerosis B-Lymphocyte Subsets B-Lymphocytes Biological Assay Blood Blood Vessels CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Calcium Cardiovascular Diseases Cardiovascular system Cause of Death Cell Communication Cell physiology Cells Cellular biology Cholesterol Cholesterol Esters Chronic Clinical Clinical Trials Coronary artery Cytometry Databases Development Disease Enzyme-Linked Immunosorbent Assay Epitopes Event Future Gender Genetic Transcription Goals Human Immune Immune Targeting Immune response Immune system Immunity Immunoglobulins Inflammatory Interleukin-1 beta Interleukin-10 Interleukin-17 Laboratories Link Lipids Lipoproteins Low-Density Lipoproteins Lymphocyte Lymphoid Tissue Measurement Metabolic Methodology Molecular Molecular Target Multi-Ethnic Study of Atherosclerosis Mus Myeloid Cells National Heart, Lung, and Blood Institute Oxides Participant Pattern Peptides Phenotype Plasma Play Predictive Value Proteins Reaction Regulation Regulatory T-Lymphocyte Risk Role Scientific Advances and Accomplishments Seminal Signal Transduction Specificity Study Subject T cell response T-Lymphocyte Testing Therapeutic adaptive immune response apolipoprotein B-100 atherogenesis atheroprotective base cardiovascular risk factor cellular targeting chemokine receptor cohort data sharing design exhaust high risk human subject immune function immunoregulation innovation lymph nodes macrophage member migration monocyte news novel therapeutics oxidized low density lipoprotein programs response success transcriptome sequencing

项目摘要

ABSTRACT In the past decade, several groups, including our own, have shown the importance of immune cell subsets on atherogenesis in mice, but we are just beginning to discover how immune cells are metabolically and transcriptionally changed during atherogenesis in humans. This PPG will focus on human cardiovascular disease, and will test the hypothesis that lipoproteins with their lipid and protein components trigger innate and adaptive immune responses that impact atherosclerosis. We will study functional changes in immune cells and the immune cell cross-talk that occurs during atherosclerosis progression in humans using the well- characterized NHLBI-sponsored longitudinal clinical cohort, Multi-Ethnic Study of Atherosclerosis (MESA), and our UVA Cardiovascular Cohort. We will study subjects who have low versus high cardiovascular risk based on their coronary artery calcium (CAC) Agatston scores. CAC Agatston scores have high positive predictive values for cardiovascular disease (CAD) events, and Agatston scores (above 300) are strong predictors of future CAD events. We will study subjects with CAC Agatston scores >300 as high risk, and we have carefully matched controls by age and gender with Agatston scores of zero as low risk. In this synergistic program, Project 1 Monocyte Subsets & Immunity in Mouse and Human Atherosclerosis, will study how monocyte subsets respond to oxidized LDL to impact cardiovascular disease. Project 2 Cholesterol Regulation of Inflammatory Macrophages in Atherosclerosis, will investigate how cholesterol modulates macrophage polarization in atherosclerosis. Project 3 B Cell Subsets in Mouse and Human Atherosclerosis, will study how specific chemokine receptors promote B cell subset migration and atheroprotection. Project 4 ApoB-Specific CD4 T cells in Mouse and Human Atherosclerosis, will test the hypothesis that apoB-specific CD4 T cells are atheroprotective by producing IL-10, but fail later in disease. An important synergistic aspect to our PPG is that B cells, T cells, monocytes and macrophages communicate with each other in the artery wall and lymphoid tissues, and each project studies one of these immune cell subsets, so there are many project interactions. Unique aspects of our program are the strong focus on studying human immune cells, the use of CyTOF mass cytometry and RNA-Seq as innovative methodologies used to study these cells, the measurement of plasma immunoglobulins using ELISA-based assays developed in our group and currently used in multiple clinical trials, and our ability to link all of our group's discoveries with a 15-year extensive MESA clinical database to understand how immune cells change to contribute to CAC progression and cardiovascular disease. The end goal of our studies is to identify novel therapeutic strategies targeting immune cell function to limit cardiovascular disease.

摘要