Internal Medicine/Cardiology and Angiology, University Hospital of Giessen and Marburg, 35033 Marburg, Germany.
Biochemical-Pharmacological Centre (BPC) Marburg, Institute of Pharmacology and Clinical Pharmacy, University of Marburg, 35043 Marburg, Germany.
Int J Mol Sci. 2020 Nov 30;21(23):9095. doi: 10.3390/ijms21239095.
Cardiac-specific JDP2 overexpression provokes ventricular dysfunction and atrial dilatation in mice. We performed in vivo studies on JDP2-overexpressing mice to investigate the impact of JDP2 on the predisposition to spontaneous atrial fibrillation (AF).
JDP2-overexpression was started by withdrawal of a doxycycline diet in 4-week-old mice. The spontaneous onset of AF was documented by ECG within 4 to 5 weeks of JDP2 overexpression. Gene expression was analyzed by real-time RT-PCR and Western blots.
In atrial tissue of JDP2 mice, besides the 3.6-fold increase of JDP2 mRNA, no changes could be detected within one week of JDP2 overexpression. Atrial dilatation and hypertrophy, combined with elongated cardiomyocytes and fibrosis, became evident after 5 weeks of JDP2 overexpression. Electrocardiogram (ECG) recordings revealed prolonged PQ-intervals and broadened P-waves and QRS-complexes, as well as AV-blocks and paroxysmal AF. Furthermore, reductions were found in the atrial mRNA and protein level of the calcium-handling proteins NCX, Cav1.2 and RyR2, as well as of connexin40 mRNA. mRNA of the hypertrophic marker gene ANP, pro-inflammatory MCP1, as well as markers of immune cell infiltration (CD68, CD20) were increased in JDP2 mice.
JDP2 is an important regulator of atrial calcium and immune homeostasis and is involved in the development of atrial conduction defects and arrhythmogenic substrates preceding paroxysmal AF.
心脏特异性 JDP2 过表达可引起小鼠心室功能障碍和心房扩张。我们对 JDP2 过表达小鼠进行了体内研究，以研究 JDP2 对自发性心房颤动（AF）易感性的影响。
在 4 周龄的小鼠中通过去除强力霉素饮食开始 JDP2 过表达。在 JDP2 过表达后 4 至 5 周内通过心电图记录自发性 AF 的发作。通过实时 RT-PCR 和 Western blot 分析基因表达。
在 JDP2 小鼠的心房组织中，除了 JDP2 mRNA 的 3.6 倍增加外，在 JDP2 过表达后的 1 周内没有检测到变化。在 JDP2 过表达 5 周后，出现了心房扩张和肥大，伴有拉长的心肌细胞和纤维化。心电图（ECG）记录显示 PQ 间隔延长，P 波和 QRS 复合体变宽，以及房室传导阻滞和阵发性 AF。此外，钙处理蛋白 NCX、Cav1.2 和 RyR2 的心房 mRNA 和蛋白水平以及 connexin40 mRNA 降低。JDP2 小鼠中肥厚标志物基因 ANP、促炎 MCP1 以及免疫细胞浸润标志物（CD68、CD20）的 mRNA 增加。
JDP2 是心房钙和免疫稳态的重要调节剂，参与了阵发性 AF 之前的心房传导缺陷和致心律失常基质的发展。
