Molecular Analysis of Atrila fibrillation - approach through Ca2+ regulatory proteins -

细胞内Ca^2+稳态异常发生在慢性心房颤动（AF）中.细胞内Ca^2+浓度受兰尼碱和1，4，5-三磷酸肌醇（IP 3）受体的调节。我们最近报道了慢性房颤心房组织中兰尼碱受体的改变。在这里，我们检查房颤患者是否有心房IP 3受体的改变。我们分析了13例二尖瓣疾病（MVD）伴AF（MVD/AF）患者、5例MVD伴正常窦性心律（MVD/NSR）患者和8例对照组NSR患者（冠状动脉旁路手术期间获得的组织）右心房心肌中IP 3受体的表达。术前获得血流动力学和超声心动图数据，并对心房组织进行免疫组织化学研究。IP 3受体在MVD/AF中的相对表达量（0.75 ± 0.26）显著高于MVD/NSR中的相对表达量（0.42 ± 0.13，p<0.05），且均显著高于对照组（0.14± 0.08）。MVD/AF组IP 3受体mRNA相对表达量（0.028±0.008）显著高于对照组（0.015±0.004，p<0.01），但MVD/AF组与MVD/NSR组（0.020±0.006）无显著性差异。左房内径≥ 40 mm、肺毛细血管楔压≥ 10 mmHg、右房压≥ 5 mmHg的患者IP 3受体蛋白和mRNA的相对表达水平较高。IP 3受体在MVD组心房肌细胞胞浆和核膜中表达明显增强。由于心房肌的慢性机械负荷增加了IP 3受体的表达，特别是在慢性AF患者中，因此IP 3受体的上调可能在调节细胞内Ca^2+稳态和启动和/或维持AF中起重要作用。

Abnormal intracellular Ca^<2+> homeostasis occurs in chronic atrial fibrillation (AF). The intracellular Ca^<2+> concentration is regulated by ryanodine and inositol 1,4,5-trisphosphate (IP3) receptors. We recently reported alterations in ryanodine receptors in atrial tissue in chronic AF. Here, we examine whether AF patients have alterations in atrial IP3 receptors. We analyzed IP3 receptor expression in the right atrial myocardium from 13 mitral valvular disease (MVD) patients with AF (MVD/AF), 5 MVD patients with normal sinus rhythm (MVD/NSR), and 8 control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue. The relative expression level of IP3 receptor was significantly greater in MVD/AF (0.75 ± 0.26) than in MVD/NSR (0.42 ± 0.13, p<0.05), and both were significantly above control (0.14± 0.08). The relative expression level of IP3 receptor mRNA was significantly greater in MVD/AF (0.028±0.008) than in control (0.015±0.004, p<0.01), but MVD/AF patients did not differ from MVD/NSR (0.020±0.006) patients. The relative expression levels of IP3 receptor protein and mRNA were higher in patients with left atrial dimension 【greater than or equal】40 mm, pulmonary capillary wedge pressure 【greater than or equal】10 mmHg, and right atrial pressure 【greater than or equal】5 mmHg. IP3 receptors were overexpressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca^<2+> homeostasis and initiating and/or perpetuating AF.