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致力于开发有效疗法的临床翻译研究科学家 适用于心血管疾病的患者。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也激发了我更好地了解分子 心外膜脂肪细胞影响心房颤动的发展的机制。我建议进行 一项前瞻性临床研究，以检验脂肪细胞正在募集髓样细胞到 心肌增加术后AF的脆弱性。我的提案的具体目的是： 目的1。表征心外膜脂肪细胞的转录组曲线，并确定循环水平 脂肪衍生的趋化因子 AIM 2。确定心外膜脂肪组织中炎症之间的关系，并留下心房功能 通过超声心动图参数评估，包括左心房体积指数，左心房函数索引和左 心房机械分散。 目标3。检查心外膜脂肪组织中的炎症与术后入射 冠状动脉搭桥手术后的AF 我正在寻求来自国家心脏肺和以患者为导向的职业发展奖的K23 血液研究所让我有机会扩大我在临床研究方法论，生物信息学方面的技能 和生物统计学，使我成为一名翻译科学家。该提案中的培训计划 课程工作的优势和强大的指导团队（McManus博士，Fitzgerald和Corvera博士） 专业知识（房颤，先天免疫，脂肪细胞生物学和临床研究方法）填充关键 在我以前的培训中，差距是为了促进我的职业目标。该建议是最早探索 将髓样细胞募集到心肌的机制。这项工作将为您提供新颖的见解 心外膜脂肪组织，炎症和术后AF之间的关联。招募 炎性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 炎症将确定术后AF的新疗法。