Investigation on the Calcineurin-Nuclear Factor of Activated T-Cell Signal Transduction Pathway in a Porcine Model of Atrial Fibrillation

• Main Authors: Chih-Chung Lin, 林志忠
• Other Authors: Ling-Ping Lai
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/75264169965673901035

碩士 === 國立臺灣大學 === 藥理學研究所 === 91 === Background Cytosolic calcium overloading occurs in atrial fibrillation tissue. We therefore investigated the calcium-activated calcineurin-nuclear factor of activated T-cell (NFAT) pathway in atrial tissue in a porcine model of atrial fibrillation. Methods and Results Atrial fibrillation was induced in adult pigs by rapid atrial pacing at a rate of 600 per minute. Atrial tissue from the left atrium was obtained 6 weeks after implantation of the pacemaker (pacing for 4 weeks and atrial fibrillation without pacing for 2 weeks). We found that calcineurin enzyme activity increased significantly in pigs with atrial fibrillation when compared to control pigs (0.143OD620 ± 0.013 vs 0.038OD620 ± 0.028, p < 0.01). We found that both NFATc3 and NFATc4, the down stream effectors of calcineurin, increased significantly in the nuclei in atrial fibrillation tissue using immunoblotting. Translocation of NFATc3 and NFATc4 into the nuclei was also demonstrated in atrial tissue microsections using immunohistochemistry. The electrophoretic mobility shift assay further demonstrated that nuclear extracts from atrial fibrillation tissue had a significantly larger binding capacity for NFAT specific oligonucleotide probes. Conclusion Our results demonstrated that calcineurin activity was increased in atrial fibrillation tissue with subsequent NFATc3 and NFATc4 translocation into the nucleus. Activation of this signal transduction pathway may play an important role in the pathogenesis of atrial fibrillation.