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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：
10670732
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/10670732
关键词：
Acceleration 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 Deterioration Development Disease Effector Cell Emerging Technologies Endowment 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 Ischemia Kinetics Label Macrophage Malignant Neoplasms Methods Modification Molecular Mus Mutation Myocardial Infarction Myocardial Ischemia Outcome Phenotype Predisposition Process Recovery Risk Risk Reduction Role Signal Transduction System Testing Tissues atherogenesis candidate validation cardiovascular disorder risk cardiovascular risk factor cell behavior cell type healing in vivo 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.

项目摘要：炎症对缺血性心血管疾病的影响已得到充分证实认可。人们普遍认为先天免疫系统的单核细胞/巨噬细胞成分是对动脉粥样硬化疾病的发生和进展至关重要。其他人的最新进展表明存在具有特定功能的特殊单核细胞亚群，并且我们有开发了可以进一步评估造血细胞内异质性的系统。我们的计划是使用新兴技术允许对异质性进行克隆评估，以解决什么问题单核细胞/巨噬细胞的特定亚群会导致动脉粥样硬化。我们将确定单核细胞/巨噬细胞是否出生时就具有动脉粥样硬化形成的先天倾向，或在发生动脉粥样硬化后获得此类特征。我们将定义此类功能属性的分子驱动因素并测试针对目标的干预措施类型单核细胞/巨噬细胞可降低进行性动脉粥样硬化的风险。