Mechanisms underlying atrial fibrillation associated with chronic kidney disease

项目总结/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因子，并且是心血管疾病的危险因素。 心房颤动（AF）的重要危险因素。关于这些疾病的分子机制， 与CKD相关的基础AF。我们的初步数据显示，在细胞内NLRP 3炎性小体的激活， CKD小鼠模型中分离的心房肌细胞。本项目的长期目标是阐明 小鼠炎症小体激活导致房颤发生的分子和细胞机制 关于CKD我们将检验心房肌内NLRP 3炎性小体激活增强的假设， 心肌细胞通过增加促钙释放， RyR 2的PEG磷酸化。

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.