Ryanodine receptor regulation in post-operative atrial fibrillation

项目总结 术后心房颤动(POAF)是心胸外科手术的常见并发症。 发病率在10%到50%之间。这种情况通常在手术后2-3天达到高峰。很少 POA的分子机制仍然是已知的，这使得POA的发展 更好的治疗方法很难。我们的初步结果表明，患者和体内激素水平降低的老鼠 心房中的“条纹肌肉优先表达的蛋白激酶”(SpeG)增加了罹患 发展POAF。这个项目的总体目标是阐明分子和细胞机制。 通过这种方式，SpeG水平降低导致细胞内钙处理和POAF改变。居万将测试 假设SpeG激酶活性降低会改变RyR2的磷酸化并促进POAF。在……里面 此外，他还将开发改进的心房特异性基因治疗载体，用于运送SpeG激酶 结构域到心房组织。这些临床前研究可能会导致以靶点为基础的 术后房颤的治疗。

PROJECT SUMMARY 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. Very little remains known about the molecular mechanisms underlying poA, which makes the development of better therapies difficult. Our preliminary results suggest that patients and mice with reduced levels of ‘Striated Muscle Preferentially Expressed Protein Kinase’ (SPEG) in the atria have an increased risk of developing poAF. The overall goal of this project is to elucidate the molecular and cellular mechanisms by which reduced SPEG levels cause altered intracellular Ca2+ handling and poAF. Juwan will test the hypothesis that reduced SPEG kinase activity alters RyR2 phosphorylation and promotes poAF. In addition, he will develop improved atrial-specific gene therapy vectors for the delivery of SPEG kinase domains to atrial tissue. These preclinical studies may lead to the development of a target-based therapy for postoperative atrial fibrillation.