Purkinje Cells and Arrhythmia Mechanisms

浦肯野细胞和心律失常机制

• 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
• 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

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的主要死亡原因。半年 这些死亡是突然发生的，通常是由于急性心肌梗塞时出现的室性快速性心律失常。 缺血、获得性心脏病或遗传综合征，包括通道病和心肌病。 专门的心脏传导系统（CCS）包括一个异质的细胞网络， 在整个心肌中电兴奋波的启动和传播。积累 有证据表明，心室传导系统功能障碍（ventricular conduction system，VES）在心肌梗死中起着关键的机制作用， 引发广泛的危及生命的室性心律失常，然而，我们的研究存在重大差距。 了解负责的形成，功能和功能障碍的分子机制， - 是的我们的实验室已经建立了新的工具，并确定了新的基因和途径，我们假设 对骨形成、功能和功能障碍至关重要。在这个应用中，我们提出了一系列的实验， 旨在测试这些新基因和途径的生物学重要性。