Purkinje Cells and Arrhythmia Mechanisms

浦肯野细胞和心律失常机制

基本信息

批准号：
9277533
负责人：
Glenn I Fishman
金额：
$ 59.15万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-01 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9277533
关键词：
Acute Adult Affect Arrhythmia B-Lymphocytes Bioinformatics Biological Assay Biological Testing CRISPR/Cas technology Calmodulin Cardiac Cardiac Myocytes Cardiac conduction system Cardiomyopathies Cardiovascular system Cause of Death Cell Adhesion Molecules Cell Cycle Cells Cessation of life ChIP-seq Clinical Clustered Regularly Interspaced Short Palindromic Repeats Data Data Set Developed Countries Developing Countries Development Disease ETV1 gene Electrophysiology (science)Functional disorder Funding Gene Expression Gene Targeting Genes Genetic Transcription Health Heart Heart Abnormalities Heart Block Heart Diseases Heart failure Heritability Human Inherited Ion Channel Ischemia Laboratories Life Link Maintenance Molecular Morbidity - disease rate Mus Mutant Strains Mice Myocardial Myocardial Contraction Myocardium Pathogenesis Pathologic Pathway interactions Periodicity Phenotype Physiology Play Proteins Purkinje Cells Reporter Reporting Research Risk Role Series Syndrome System Systems Biology Systems Development Tachyarrhythmias Tamoxifen Testing Transactivation United States Variant Ventricular Ventricular Arrhythmia Ventricular Dysfunction Ventricular Function Ventricular Tachycardia Withdrawal Work calmodulin-dependent protein kinase II clinically relevant comparative contactin design experimental study falls gene function genetic regulatory protein heart rhythm human disease innovation insight loss of function loss of function mutation novel phenome receptor recombinase stressor sudden cardiac death targeted treatment tool transcription factor transcriptome

项目摘要

PROJECT SUMMARY Heart disease remains the leading cause of death in the United States and other developed countries. Half of these deaths occur suddenly, typically from ventricular tachyarrhythmias that arise in the setting of acute ischemia, acquired heart disease or inherited syndromes including channelopathies and cardiomyopathies. The specialized cardiac conduction system (CCS) comprises a heterogeneous network of cells that orchestrate the initiation and propagation of a wave of electrical excitation throughout the myocardium. Accumulating evidence suggests that dysfunction of the ventricular conduction system (VCS) plays a key mechanistic role triggering a broad range of life-threatening ventricular arrhythmias, however major gaps exist in our understanding of the molecular mechanisms responsible for the formation, function and dysfunction of the VCS. Our laboratory has established new tools and identified novel genes and pathways that we hypothesize are critical for VCS formation, function and dysfunction. In this application we propose a series of experiments designed to test the biological importance of these new genes and pathways.

项目摘要心脏病仍然是美国和其他发达国家死亡的主要原因。一半这些死亡突然发生，通常来自急性环境中出现的心室心律失常缺血，心脏病或遗传性综合症，包括通道病和心肌病。专门的心脏传导系统（CCS）包括一个编排的细胞网络整个心肌的电激发浪的启动和传播。累积有证据表明，心室传导系统（VC）的功能障碍起关键机械作用引发广泛的威胁生命的心室心律不齐，但是我们的主要差距存在了解负责导致形成，功能和功能障碍的分子机制 VCS。我们的实验室已经建立了新工具并确定了我们假设的新型基因和途径对于VC形成，功能和功能障碍至关重要。在此应用中，我们提出了一系列实验旨在测试这些新基因和途径的生物学重要性。