Role of epicardial adiposity as a local mediator of VT/VF dynamics in donor human hearts

心外膜脂肪作为供体心脏中 VT/VF 动态局部调节因素的作用

基本信息

批准号：
10770117
负责人：
Kedar Kirtikumar Aras
金额：
$ 24.87万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-10 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10770117
关键词：
Adipose tissue Anatomy Anti-Inflammatory Agents Arrhythmia Bioinformatics Body mass index Calcium Cardiac Catecholamines Categories Clinical Coupling Data Development Down-Regulation Experimental Designs Fatty acid glycerol esters Future Genetic Transcription Healthcare Systems Heart Heart failure Human Hyperactivity IL6 gene Incidence Inflammation Inflammatory Interleukin-6 Isoproterenol Knowledge Link Maps Mediating Mediator Mentors Molecular Morbidity - disease rate Obesity Optics Organ Overweight Paracrine Communication Phase Physiological Play Predisposition Prevalence Risk Risk Factors Role Site Stimulus Tachyarrhythmias Testing Tissues Toll-like receptors Training Up-Regulation Ventricular Ventricular Arrhythmia Ventricular Fibrillation Ventricular Premature Complexes Ventricular Tachycardia Western Blotting adipocyte biology adiponectin calmodulin-dependent protein kinase II cytokine experimental study insight mortality multimodality next generation sequencing novel marker obesity treatment paracrine sudden cardiac death transcriptome transcriptome sequencing

项目摘要

Project Summary: Ventricular tachyarrhythmias are responsible for 300,000 sudden cardiac deaths a year in the US. The mechanisms underlying these arrhythmias in the majority of cases are ventricular tachycardia (VT) and/or ventricular fibrillation (VF). The ever-increasing prevalence of obesity also poses a significant burden on the health care system with increased morbidity and mortality. Importantly, obesity has been associated with cardiac arrhythmias with increased risk of sudden cardiac death linked to increased adiposity. However, the mechanisms by which obesity could result in ventricular arrhythmias (VT/VF) remain incompletely understood. In this proposal, I plan to use a multimodal and multiscale approach to characterize VT/VF in donor human hearts associated with sustained obesity. In the mentored phase of this project, I will use donor hearts to investigate the role of epicardial adiposity in promoting VT/VF via paracrine signaling, while also getting specialized training in bioinformatics and adipocyte biology. In the independent phase of this project, I will use donor hearts to investigate the role of epicardial adiposity in generating arrhythmogenic triggers. The experiments outlined below will advance our understanding of VT/VF mechanisms and also serve as proof-of-concept for future experiments designed to develop new markers to predict and treat VT/VF vulnerability in a clinical setting.

项目概要：在美国，室性快速心律失常每年导致 300,000 例心源性猝死。这大多数情况下，这些心律失常的潜在机制是室性心动过速 (VT) 和/或心室颤动（VF）。日益增加的肥胖患病率也给人们带来了沉重的负担医疗保健系统的发病率和死亡率不断增加。重要的是，肥胖与心律失常与肥胖增加相关的心源性猝死风险增加。然而，肥胖导致室性心律失常（VT/VF）的机制仍然存在不完全理解。在这个提案中，我计划使用多模式和多尺度的方法来描述与持续肥胖相关的供体心脏中的 VT/VF 特征。在辅导阶段在这个项目中，我将使用捐赠心脏来研究心外膜肥胖在促进 VT/VF 中的作用旁分泌信号传导，同时还接受生物信息学和脂肪细胞生物学方面的专门培训。在在这个项目的独立阶段，我将使用捐赠心脏来研究心外膜肥胖在产生致心律失常的触发因素。下面概述的实验将加深我们的理解 VT/VF 机制，也可作为未来实验的概念验证，旨在开发新的在临床环境中预测和治疗 VT/VF 脆弱性的标记物。