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T-cell regulation of cardiac remodeling

T细胞对心脏重塑的调节

基本信息

批准号：
10582516
负责人：
Kristine Y DeLeon-Pennell
金额：
--
依托单位：
RALPH H JOHNSON VA MEDICAL CENTER
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：
2017-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10582516
关键词：
Admission activity Adverse effects Aging Apoptosis CASP3 gene CD36 gene CD44 gene CD8-Positive T-Lymphocytes CD8B1 gene Cardiac Cardiovascular Diseases Cardiovascular system Cell Count Cell secretion Cells Chronic Chronic Disease Cohort Studies Coupled Development Event Feedback Foundations Functional disorder Future Gelatinase B General Population Goals Grant Health Healthcare Healthcare Systems Heart failure ITGAM gene Impairment In Vitro Incidence Inflammation Inflammatory Innate Immune Response Intervention Knowledge Left Ventricular Remodeling Left ventricular structure Long-Term Effects Matrix Metalloproteinases Mediating Mission Molecular Mus Myocardial Infarction Myocardial rupture Outcome Study Patients Pattern Peroxidases Personal Satisfaction Phenotype Physiology Population Proteomics Research Personnel Resolution Rest Role SELL gene Solid Source System T cell differentiation T cell regulation T-Cell Activation T-Lymphocyte TNF gene Time Tissues Training Veterans adaptive immune response adaptive immunity cardiogenesis clinical practice cohort coronary fibrosis cytokine effector T cell experimental study first responder heart function high risk improved in vivo innovation interdisciplinary approach mortality neutrophil prevent response therapeutic target virtual wound healing

项目摘要

Veterans have 2-times higher risk of developing cardiovascular disease compared to non-veterans. For veterans who have a heart attacked (myocardial infarction; MI), 1 in 3 will not survive 1 year after the event compared to 1 in 10 in the general population. The goal of my project is to understand how the wound healing response after MI can promote the development of heart failure. My focus is the innate immune response, specifically the role of CD8+ T-cells. My central hypothesis is that CD8+ effector T- cells regulate PMN physiology through MMP-9 to induce adverse remodeling post-MI. Aim 1 will determine the role of CD8+ T-cells on the neutrophil physiology using cellular proteomics coupled with ex vivo experiments. Aim 2 will determine the role CD8+ T-cells in vivo focusing on how CD8+ T-cell effector subtypes and the secretion of MMP-9 effect long term cardiac function and survival post-MI. This is the first proposal to integrate multidisciplinary approaches to evaluate CD8+ T-cells in the MI setting. This study will add to our understanding of critical mechanisms underlying adverse effects of the adaptive immune response and wound healing after MI. The proposed study aligns with the mission of the VA Healthcare System by providing molecular knowledge to clinical practices so that the VA Healthcare System can continue to provide exceptional health care that improves Veteran health and well-being.

退伍军人患心血管疾病的风险是非退伍军人的2倍。为有心脏病发作（心肌梗死; MI）的退伍军人，三分之一在心脏病发作后一年内无法生存。相比之下，一般人群中为1/10。我的项目的目标是了解心肌梗死后的伤口愈合反应可促进心力衰竭的发展。我关注的是免疫反应，特别是CD 8 + T细胞的作用。我的中心假设是CD 8+效应T- 细胞通过MMP-9调节PMN生理学以诱导MI后的不利重构。目标1将使用细胞蛋白质组学结合免疫细胞化学，离体实验。目的2将确定CD 8 + T细胞在体内的作用，重点是CD 8 + T细胞如何在体内发挥作用。效应子亚型和MMP-9的分泌影响MI后的长期心脏功能和存活。这是第一个建议整合多学科的方法来评估CD 8 + T细胞在MI设置。这项研究将增加我们对适应性环境不良影响的关键机制的理解。 MI后免疫应答和伤口愈合。拟议的研究与VA的使命一致通过为临床实践提供分子知识，系统可以继续提供特殊的医疗保健，改善退伍军人的健康和福祉。