T-cell regulation of cardiac remodeling

T细胞对心脏重塑的调节

• 批准号: 10266004
• 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
• 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/10266004
• 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

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两倍。为 有心脏病发作(心肌梗死；MI)的退伍军人，1/3将不能在1年后存活 相比之下，普通人群中每10人中就有1人发生这种情况。我这个项目的目标是了解 心肌梗死后创面愈合反应可促进心力衰竭的发展。我关注的是与生俱来的 免疫反应，特别是CD8+T细胞的作用。我的中心假设是CD8+效应器T- 细胞通过基质金属蛋白酶-9调节中性粒细胞的生理功能，诱导心肌梗死后的不良重构。目标1将 细胞蛋白质组学联合检测CD8+T细胞在中性粒细胞生理中的作用 体外实验。目标2将确定CD8+T细胞在体内的作用，重点研究CD8+T细胞如何 效应器亚型和基质金属蛋白酶-9的分泌影响心肌梗死后的长期心功能和生存。这 是第一个整合多学科方法来评估心肌梗死患者CD8+T细胞的提案。 这项研究将增加我们对适应性疾病不良影响的关键机制的理解。 心肌梗死后的免疫反应与创面愈合。拟议的研究与退伍军人事务部的使命一致 通过向临床实践提供分子知识，使VA Healthcare 系统可以继续提供卓越的医疗保健，改善退伍军人的健康和福祉。