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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

基本信息

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
项目类别：
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

项目摘要

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)是心血管疾病发病率和死亡率的已知预测因子，是一种房颤的重要危险因素。目前对其分子机制知之甚少。与CKD相关的潜在房颤。我们的初步数据显示NLRP3炎症体在慢性肾脏病小鼠模型中分离的心房肌细胞。这个项目的长期目标是阐明炎性小体激活致小鼠房颤发生的分子和细胞机制与CKD合作。我们将验证这样一种假设，即心房内NLRP3炎症小体的激活增强心肌细胞通过增加钙离子释放促进诱发心律失常的钙离子释放，增强房颤的易感性 SpeG-RyR2的磷酸化。