The Role of ERBB4 in Atrial Electrophysiology and Atrial Fibrillation

ERBB4 在心房电生理学和心房颤动中的作用

• 批准号: 10671524
• 负责人: David S Park
• 金额: $ 42.38万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10671524
• 关键词: Address; Adult; Aging; Arrhythmia; Atrial Fibrillation; Biological Models; Calcium; Candidate Disease Gene; Cardiac; Cardiac Electrophysiologic Techniques; Cardiac Myocytes; Cardiovascular system; Cause of Death; Cell Line; Data; Defect; Dependence; Development; Disease; Down-Regulation; ERBB2 gene; ETV1 gene; Electrophysiology (science); Environment; ErbB4 gene; Evaluation; Functional disorder; Gene Dosage; Genes; Genetic Transcription; Heart; Heart Abnormalities; Heart Atrium; Heart Diseases; Heart failure; Histologic; Human; Hypertension; Ion Channel; Knockout Mice; Knowledge; Left; Left atrial structure; Link; MAPK3 gene; Maintenance; Maps; Medical; Modeling; Molecular; Morbidity - disease rate; Mus; Muscle Cells; Mutant Strains Mice; Myocardium; Neuregulin 1; Neuregulin Receptor; Nodal; Optics; Pathogenesis; Pathway interactions; Patients; Physiological; Physiology; Predisposition; Prevalence; Process; Proteins; Public Health; Receptor Protein-Tyrosine Kinases; Research; Risk; Role; Signal Pathway; Signal Transduction; Sodium; Stroke; Structure; Susceptibility Gene; System; Tamoxifen; Therapeutic; Therapeutically Targetable; Transcriptional Activation; Transgenic Mice; Tretinoin; acquired factor; calmodulin-dependent protein kinase II; cardiogenesis; defined contribution; effective therapy; erbB-2 Receptor; gene regulatory network; genetic risk factor; genome wide association study; heart rhythm; hospital utilization; mortality; mouse model; postnatal; programs; side effect; stroke incidence; success; targeted treatment; transcription factor; transcriptome; transcriptomics

PROJECT SUMMARY Atrial fibrillation (AF) is the leading cause of stroke and a major cause of morbidity and mortality in the US. AF is due to both inherited and acquired factors. Genome-wide association studies have identified ERBB4 as a candidate susceptibility gene for AF. Acquired conditions, such as aging, hypertension, and heart failure, are known to cause electrical and structural changes in the left atrium (LA) in a process known as remodeling that predisposes to AF. Our data show that left atrial ERBB4 levels are reduced in patients with AF. We have also shown that ErbB4 is downregulated in heart disease mouse models. To study the role of ErbB4 in both atrial electrical development and in acquired AF mechanisms, we have generated mouse models that have reduced ErbB4 expression during development or acquired during adulthood. Both model systems show an important dependency of correct ErbB4 gene dosage in the maintenance of normal atrial electrophysiology.

项目摘要 心房颤动（AF）是中风的主要原因，也是美国发病率和死亡率的主要原因。 AF是 由于继承和获得的因素。全基因组关联研究已将ERBB4鉴定为 AF的候选敏感性基因。衰老，高血压和心力衰竭等获得的条件是 已知会在称为重塑的过程中引起左心房（LA）的电气和结构变化 易于AF。我们的数据表明，AF患者左心房ERBB4水平降低。我们也有 表明ERBB4在心脏病小鼠模型中被下调。研究ERBB4在两个心房中的作用 电气开发以及在获得的AF机制中，我们生成了降低的鼠标模型 ERBB4在开发过程中的表达或成年期获得。两种模型系统都显示一个重要的 正确的ERBB4基因剂量的依赖性在正常心房生理学的维持中。