Ryanodine receptor regulation in post-operative atrial fibrillation

项目摘要 术后房颤（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第2-3天达到高峰。很少 仍然知道poA的分子机制，这使得发展 更好的治疗很难。我们的初步结果表明，患者和小鼠的水平降低， 心房中的“横纹肌前体表达蛋白激酶”（SPEG）增加了 开发POAF。本项目的总体目标是阐明分子和细胞机制 通过该途径，降低的SPEG水平引起改变的细胞内Ca 2+处理和poAF。朱万将测试 这一假说认为，降低SPEG激酶活性改变RyR 2磷酸化并促进poAF。在 此外，他将开发改进的心房特异性基因治疗载体，用于递送SPEG激酶 域到心房组织。这些临床前研究可能会导致开发一种基于靶向的 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.