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临床转化研究科学家，专注于开发有效的治疗方法。 对于心血管疾病患者。我在脂肪组织发育和生理学方面的背景 以及心血管医学的临床训练促使我更好地理解 心外膜脂肪细胞影响房颤发生的机制。我提议 一项前瞻性临床研究，以检验脂肪细胞正在招募髓样细胞的假设， 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学特征，并确定 脂肪源性趋化因子 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收缩功能指数。 心房机械离散度。 目标3.检查心外膜脂肪组织炎症与术后事件的关系 冠状动脉旁路移植术后房颤 我正在寻求K23辅导病人为导向的职业发展奖从国家心肺和 血液研究所让我有机会扩大我在临床研究方法学，生物信息学， 和生物统计学，使我成为一名转化科学家。本建议书中的培训计划 课程的优势和强大的辅导团队（博士麦克马纳斯，菲茨杰拉德，和Corvera）与广泛的 专业知识（房颤，先天免疫，脂肪细胞生物学和临床研究方法），以填补关键 我以前的培训中的差距，以推进我的职业目标。这一建议是第一批探索 骨髓细胞被募集到心肌的机制。这项工作将提供新的见解， 心外膜脂肪组织、炎症和术后AF之间的关系。 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 炎症将为术后AF确定新的治疗方法。