Department of Cardiac Surgery, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, Sigmund Freud Str. 25, 53127, Bonn, Germany.
Sci Rep. 2018 May 8;8(1):7145. doi: 10.1038/s41598-018-25147-8.
Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.
室性心动过速（VT）是心肌梗死后最常见且潜在致命的并发症。纠正折返所依赖的传导非均一性的生物学矫正可能是梗死治疗的重大进展。由于梗死组织的传导仅轻微增加就会显著影响 VT 的易感性，我们推断在正在愈合的梗死区内非兴奋细胞之间增强电信号的传播可能是降低梗死后心律失常风险的一种简单方法。因此，我们测试了慢病毒介导的间隙连接蛋白 43（Cx43）在急性心肌损伤中的传递。Cx43 在疤痕中的成纤维细胞和 CD45 细胞中表达，并在体内提供了显著且持久的抗心律失常保护。Cx43 注射心脏的光学映射显示疤痕内的传导速度增强，表明 Cx43 介导了心肌细胞和成纤维细胞之间的电偶联。因此，Cx43 基因治疗通过对非心肌细胞的直接体内转导，构成了一种简单且临床适用的生物治疗方法，可显著降低梗死后 VT 的发生。
