Mechanisms underlying atrial fibrillation associated with chronic kidney disease

与慢性肾脏病相关的心房颤动的机制

• 批准号: 9913385
• 负责人: Na Li
• 金额: $ 51.06万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913385
• 关键词: Adult; Affect; American; Arrhythmia; Atrial Fibrillation; CASP1 gene; Calcium; Cardiac; Cardiac Myocytes; Cardiovascular system; Chronic Kidney Failure; Confocal Microscopy; Data; Dependovirus; Development; Diagnosis; Dietary Proteins; Electric Stimulation; Electrocardiogram; Event; Exhibits; Goals; Heart Atrium; Hemorrhage; Incidence; Inflammasome; Inflammation; Ischemic Stroke; Knock-in Mouse; Knockout Mice; Measures; Mediating; Molecular; Monitor; Morbidity - disease rate; Mus; Muscle Cells; Nephrectomy; Pathogenesis; Pathway interactions; Patients; Pharmacology; Phosphorylation; Phosphorylation Site; Play; Predisposition; Prevalence; Prevention strategy; Proteins; Public Health; Risk; Risk Factors; Rodent Model; Role; Ryanodine Receptor Calcium Release Channel; Sinus; Site; Source; Sterility; Striated Muscles; Telemetry; Testing; Tissues; Work; cardiovascular risk factor; cohort; dietary manipulation; genetic regulatory protein; knock-down; mortality; mouse model; novel; patch clamp; prevent; receptor; receptor expression; targeted treatment; treatment strategy

PROJECT SUMMARY / ABSTRACT Chronic kidney disease (CKD) is a known predictor of cardiovascular morbidity and mortality, and is an important risk factor for atrial fibrillation (AF). Very little remains known about the molecular mechanisms underlying AF associated with CKD. Our preliminary data reveal activation of the NLRP3 inflammasome within atrial myocytes isolated in a mouse model of CKD. The long-term goal of this project is to elucidate the molecular and cellular mechanisms underlying AF development as a result of inflammasome activation in mice with CKD. We will test the hypothesis that enhanced activation of the NLRP3 inflammasome within atrial myocytes enhances the susceptibility to AF by promoting proarrhythmogenic Ca2+ releases via increased SPEG-phosphorylation of RyR2.

项目摘要 /摘要 慢性肾脏疾病（CKD）是心血管发病率和死亡率的已知预测指标，是一种 房颤的重要危险因素（AF）。关于分子机制的知之甚少 与CKD相关的基础AF。我们的初步数据揭示了NLRP3炎症体的激活 在CKD的小鼠模型中分离出的心肌细胞。该项目的长期目标是阐明 由于小鼠炎症体激活AF的发展的分子和细胞机制 与CKD。我们将测试以下假设，即心房内NLRP3炎症体的激活增强 肌细胞通过增加促进心律失常Ca2+释放来增强对AF的敏感性 RYR2的SPEG磷酸化。