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.

与非退伍军人相比，退伍军人患心血管疾病的风险高2倍。为了心脏袭击的退伍军人（心肌梗塞； MI），三分之一将无法生存1年。事件与普通人群中的十分之一相比。我项目的目的是了解 MI后的伤口愈合反应可以促进心力衰竭的发展。我的重点是先天免疫反应，特别是CD8+ T细胞的作用。我的中心假设是CD8+效应t- 细胞通过MMP-9调节PMN生理，以诱导MI后不良重塑。目标1意志确定CD8+ T细胞在中性粒细胞生理学上的作用，使用细胞蛋白质组学与离体实验。 AIM 2将确定体内CD8+ T细胞的作用，重点是CD8+ T细胞效应子亚型和MMP-9的分泌效果长期心脏功能和MI后生存。这是整合多学科方法来评估MI环境中CD8+ T细胞的第一个建议。这项研究将增加我们对适应性不利影响的关键机制的理解 MI后免疫反应和伤口愈合。拟议的研究与VA的任务保持一致医疗保健系统通过为临床实践提供分子知识，以便VA医疗保健系统可以继续提供卓越的医疗保健，从而改善退伍军人的健康和福祉。