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Project 1: Implications of blood cell heterogeneity for CV disease

项目 1：血细胞异质性对心血管疾病的影响

基本信息

批准号：
10469350
负责人：
David T Scadden
金额：
$ 39.28万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10469350
关键词：
Address Affect Age Animals Arterial Fatty Streak Arteries Atherosclerosis Behavior Blood Blood Cells CRISPR/Cas technology Cardiac Cardiovascular Diseases Cells Clonal Hematopoietic Stem Cell Collaborations Development Disease Effector Cell Emerging Technologies Epigenetic Process Heart Injuries Heart failure Hematopoiesis Hematopoietic Hematopoietic System Hematopoietic stem cells Heterogeneity Human Individual Infarction Inflammation Inflammatory Injury Innate Immune System Instruction Intervention Kinetics Label Methods Modification Molecular Mus Mutation Myocardial Infarction Outcome Phenotype Predisposition Process Recovery Risk Role Signal Transduction System Testing Tissues atherogenesis base cardiovascular disorder risk cardiovascular risk factor cell behavior cell type healing in vivo macrophage member monocyte mouse model premalignant prevent progenitor repaired resilience single cell analysis synergism tool

项目摘要

PROJECT SUMMARY: The contributions of inflammation to ischemic cardiovascular disease has been well recognized. It is generally thought that monocyte/macrophage components of the innate immune system are central to the initiation and progression of atherosclerotic disease. Recent developments by others have suggested that there are specialized subsets of monocytic cells with particular functions and we have developed systems that can further assess heterogeneity within hematopoietic cells. Our plan is to use the emerging technologies that permit clonal assessments of heterogeneity to address the question of what specific subsets of monocyte/macrophages drive atherosclerosis. We will determine if monocyte/macrophages are born with endowed predisposition to atherogenesis or acquire such features after arrival at an atheroma. We will define molecular drivers of such functional attributes and test types of interventions targeting monocyte/macrophages to reduce the risk of progressive atherosclerosis.

项目总结：炎症对缺血性心血管疾病的作用已经得到了很好的证实。认可.通常认为先天免疫系统的单核细胞/巨噬细胞成分是免疫系统的重要组成部分。对动脉粥样硬化疾病的发生和发展至关重要。其他国家最近的事态发展这表明，有专门的单核细胞亚群具有特定的功能，我们有开发的系统可以进一步评估造血细胞内的异质性。我们的计划是利用新兴的技术，允许异质性的克隆评估，以解决什么问题，单核细胞/巨噬细胞的特定亚群驱动动脉粥样硬化。我们将确定单核细胞/巨噬细胞天生就具有动脉粥样化的倾向或在到达动脉粥样化后获得这些特征。我们将定义这些功能属性的分子驱动因素，并测试针对这些功能属性的干预措施的类型。单核细胞/巨噬细胞，以降低进行性动脉粥样硬化的风险。