Ryanodine receptor regulation in post-operative atrial fibrillation

项目总结/摘要 术后房颤（poAF）是心胸外科手术的常见并发症， 在10%到50%之间。这种情况通常在手术后第2 - 3天达到高峰，并且与以下因素有关： 住院时间过长、中风风险增加以及患者发病率增加。尽管进步 虽然对AF的发病机制的了解已经取得了很大进展，但对AF的发病机制仍知之甚少。 POAF的分子机制我们的初步数据显示，在细胞内钙处理的干扰， POAF患者的心房活检。Ryanodine受体Ca释放通道活性增加， 发现于poAF患者的心房肌细胞和一种新型的poAF小鼠模型。我们的数据表明 增强的RyR2活性是由改变的横纹肌前胶原表达蛋白水平引起的 POAF患者和小鼠心房中的"激酶"（SPEG）。本项目的长期目标是阐明 POAF发展的分子和细胞机制。我们将检验一个假设， 由于改变的SPEG磷酸化，通过RyR2释放Ca导致对poAF的易感性增强。

PROJECT SUMMARY / ABSTRACT Postoperative atrial fibrillation (poAF) is a common complication of cardiothoracic surgery with an incidence between 10 and 50%. This condition typically peaks on day 2-3 following surgery, and is associated with excessive hospitalization time, increased risk of stroke, and an increase in patient morbidity. Whereas progress has been made towards understanding the pathogenesis of AF in general, very little remains known about the molecular mechanisms underlying poAF. Our preliminary data reveal perturbed intracellular Ca handling in atrial biopsies from patients with poAF. Increased activity of the ryanodine receptor Ca release channel was found in atrial myocytes of patients with poAF and a novel mouse model of poAF. Our data suggest that enhanced RyR2 activity is caused by altered levels of `Striated Muscle Preferentially Expressed Protein Kinase' (SPEG) in atria of patients and mice with poAF. The long-term goal of this project is to elucidate the molecular and cellular mechanisms underlying poAF development. We will test the hypothesis that abnormal Ca release via RyR2 due to altered SPEG phosphorylation causes enhanced susceptibility to poAF.