Yamada Kathryn A, Rogers Joseph G, Sundset Rune, Steinberg Thomas H, Saffitz Jeffrey E
Department of Medicine (Cardiovascular Division), Center for Cardiovascular Research, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
J Cardiovasc Electrophysiol. 2003 Nov;14(11):1205-12. doi: 10.1046/j.1540-8167.2003.03276.x.
Heart failure is associated with reduced expression of the major gap junction protein connexin43 (Cx43), which may contribute to arrhythmias and sudden cardiac death in this patient population. Other cardiac connexins may be altered as well. Because connexin45 (Cx45) has been shown to colocalize with Cx43, we determined whether the number, size, or distribution of Cx45 gap junctions is altered in the failing heart.
Cx45 expression levels were measured by immunoblotting and quantitative immunostaining in failing and control human left ventricles. Total Cx45 protein was significantly (P = 0.021) up-regulated 1.8-fold in failing hearts. Cx45 immunohistochemical signal was increased by 80% (P = 0.005) due to a 3.5-fold increase in the number of gap junctions containing Cx45. Cx45 mRNA was not altered in failing hearts, suggesting reduced degradation of Cx45 protein in the failing heart. Cx43 signal, on the other hand, was reduced by 49% in failing hearts. Double-label experiments demonstrated colocalization of Cx45 and Cx43 in the same gap junctions.
Cx45 is markedly enhanced in the failing heart. Up-regulation of Cx45 in conjunction with down-regulation of Cx43 could result in abnormal impulse propagation and generation of ventricular arrhythmias, thereby predisposing patients in heart failure to sudden cardiac death.
心力衰竭与主要缝隙连接蛋白连接蛋白43（Cx43）的表达降低有关，这可能导致该患者群体出现心律失常和心源性猝死。其他心脏连接蛋白也可能发生改变。由于连接蛋白45（Cx45）已被证明与Cx43共定位，我们确定了在衰竭心脏中Cx45缝隙连接的数量、大小或分布是否发生改变。
通过免疫印迹和定量免疫染色检测衰竭和对照人左心室中Cx45的表达水平。在衰竭心脏中，总Cx45蛋白显著上调（P = 0.021），为对照的1.8倍。由于含Cx45的缝隙连接数量增加3.5倍，Cx45免疫组化信号增加80%（P = 0.005）。衰竭心脏中Cx45 mRNA未改变，提示衰竭心脏中Cx45蛋白降解减少。另一方面，衰竭心脏中Cx43信号减少49%。双标记实验证明Cx45和Cx43在同一缝隙连接中共定位。
衰竭心脏中Cx45明显增强。Cx45上调与Cx43下调相结合可能导致异常冲动传导和室性心律失常的发生，从而使心力衰竭患者易发生心源性猝死。
