The Role of Highly inflamed Epicardial Adipose Tissue in the Development of Atrial Fibrillation

高度炎症的心外膜脂肪组织在心房颤动发展中的作用

• 批准号: 10526040
• 负责人: Khanh-Van Thi Tran
• 金额: $ 16.2万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10526040
• 关键词: Adipocytes; Adipose tissue; Anti-Inflammatory Agents; Atrial Fibrillation; Award; Bioinformatics; Biometry; Biopsy Specimen; Blood specimen; CXCL10 gene; CXCL14 gene; Cardiac; Cardiac Myocytes; Cardiac Surgery procedures; Cardiovascular Diseases; Cardiovascular system; Cell Density; Cell Lineage; Cells; Clinical; Clinical Research; Clinical Trials; Coronary Artery Bypass; Data; Dendritic Cells; Development; Dexamethasone; Disease; Double-Blind Method; Electrophysiology (science); Enrollment; Fatty acid glycerol esters; Foundations; Funding; Goals; Heart Atrium; Histologic; IL18 gene; ITGAX gene; Immune; Infiltration; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Integral Membrane Protein; K-Series Research Career Programs; Left; Left Atrial Function; Left atrial structure; Length of Stay; Measures; Mechanics; Mediating; Medicine; Mentors; Molecular; Myeloid Cells; Myocardial; Myocardium; National Heart, Lung, and Blood Institute; Natural Immunity; Non-Steroidal Anti-Inflammatory Agents; Operative Surgical Procedures; Participant; Patient-Focused Outcomes; Patients; Physicians; Physiology; Plasma; Play; Postoperative Period; Prevalence; Prevention; Prevention therapy; Process; Proteomics; Randomized; Recurrence; Research; Research Design; Research Methodology; Role; Scientist; Severities; Signal Pathway; Steroids; Testing; Training; Translational Research; Work; adipocyte biology; career; chemokine; clinical investigation; cytokine; effective therapy; electrical property; experience; heart rhythm; hemodynamics; indexing; insight; macrophage; monocyte; mortality; neutrophil; novel; patient oriented; prospective; public health relevance; recruit; skills; stroke risk; transcriptomics; translational scientist

Project Abstract My long-term goal is to be a clinical-translational research scientist focused on developing effective therapies for patients with cardiovascular disease. My background in the development and physiology of adipose tissue as well as clinical training in cardiovascular medicine have motivated me to better understand the molecular mechanisms by which epicardial adipocytes influence the development of atrial fibrillation. I propose to conduct a prospective clinical investigation to test the hypothesis that adipocytes are recruiting myeloid cells to the myocardium to increase vulnerability for postoperative AF. The specific aims of my proposal are: Aim 1. Characterize transcriptomic profiles of epicardial adipocytes and determine circulating levels of adipose-derived chemokines Aim 2. Determine the relationship between inflammation in epicardial adipose tissue and left atrial function as assessed by echocardiographic parameters, including left atrial volume index, left atrial function index and left atrial mechanical dispersion. Aim 3. Examine the relationship between inflammation in epicardial adipose tissue and incident postoperative AF after coronary artery bypass graft surgery I am seeking a K23 Mentored Patient-Oriented Career Development Award from the National Heart Lung and Blood Institute allow me the opportunities to expand my skills in clinical research methodologies, bioinformatics and biostatistics and enable me to be a translational scientist. The training plan in this proposal takes advantage of coursework and a strong mentoring team (Drs. McManus, Fitzgerald, and Corvera) with broad expertise (atrial fibrillation, innate immunity, adipocyte biology and clinical research methodologies) to fill key gaps in my previous training to advance my career goals. This proposal is among the first to explore the mechanism by which myeloid cells are recruited to the myocardium. This work will provide novel insights into the association between epicardial adipose tissue, inflammation and postoperative AF. The recruitment of inflammatory cells is key to the subsequent immune-mediated dysregulation of the electrical properties in cardiomyocytes and the downstream fibrotic processes. Understanding the molecular mediators of inflammation will identify new treatments for postoperative AF.

项目摘要 我的长期目标是成为一名专注于开发有效疗法的临床转化研究科学家 对于患有心血管疾病的患者。我在脂肪组织的发育和生理学方面的背景 以及心血管医学的临床培训促使我更好地了解分子 心外膜脂肪细胞影响心房颤动发展的机制。我建议进行 一项前瞻性临床研究，旨在检验脂肪细胞正在招募骨髓细胞的假设 心肌增加术后 AF 的脆弱性。我的建议的具体目标是： 目标 1. 表征心外膜脂肪细胞的转录组谱并确定循环水平 脂肪来源的趋化因子 目标 2. 确定心外膜脂肪组织炎症与左心房功能之间的关系 通过超声心动图参数进行评估，包括左心房容积指数、左心房功能指数和左心房功能指数。 心房机械分散。 目标 3. 检查心外膜脂肪组织炎症与术后事件之间的关系 冠状动脉搭桥手术后房颤 我正在寻求国家心肺学院颁发的 K23 指导的以患者为中心的职业发展奖，并且 血液研究所让我有机会扩展我在临床研究方法、生物信息学方面的技能 和生物统计学，使我成为一名转化科学家。本提案中的培训计划采取 课程作业和强大的指导团队（麦克马纳斯博士、菲茨杰拉德和科维拉博士）的优势 填补关键领域的专业知识（心房颤动、先天免疫、脂肪细胞生物学和临床研究方法） 我之前的培训中存在差距，以推进我的职业目标。该提案是第一个探索 骨髓细胞募集到心肌的机制。这项工作将为以下方面提供新颖的见解 心外膜脂肪组织、炎症和术后房颤之间的关联。招聘 炎症细胞是随后免疫介导的电特性失调的关键 心肌细胞和下游纤维化过程。了解分子介质 炎症将确定术后 AF 的新治疗方法。