Leon H. Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, 10016, USA.
Sci Rep. 2020 Feb 13;10(1):2617. doi: 10.1038/s41598-020-59449-7.
Cardiac pathologies associated with arrhythmic activity are often accompanied by inflammation. The contribution of inflammatory cells to the electrophysiological properties of injured myocardium is unknown. Myocardial scar cell types and intercellular contacts were analyzed using a three-dimensional reconstruction from serial blockface scanning electron microscopy data. Three distinct cell populations were identified: inflammatory, fibroblastic and endocardial cells. While individual fibroblastic cells interface with a greater number of cells, inflammatory cells have the largest contact area suggesting a role in establishing intercellular electrical connections in scar tissue. Optical mapping was used to study the electrophysiological properties of scars in fetal liver chimeric mice generated using connexin43 knockout donors (bmpKO). Voltage changes were elicited in response to applied current pulses. Isopotential maps showed a steeper pattern of decay with distance from the electrode in scars compared with uninjured regions, suggesting reduced electrical coupling. The tissue decay constant, defined as the distance voltage reaches 37% of the amplitude at the edge of the scar, was 0.48 ± 0.04 mm (n = 11) in the scar of the bmpCTL group and decreased 37.5% in the bmpKO group (n = 10). Together these data demonstrate inflammatory cells significantly contribute to scar electrophysiology through coupling mediated at least partially by connexin43 expression.
与心律失常活动相关的心脏病变常伴有炎症。炎症细胞对损伤心肌的电生理特性的贡献尚不清楚。利用来自连续块面扫描电子显微镜数据的三维重建，分析了心肌瘢痕细胞类型和细胞间接触。鉴定出三种不同的细胞群：炎症细胞、成纤维细胞和成心内膜细胞。虽然单个成纤维细胞与更多的细胞相接触，但炎症细胞具有最大的接触面积，表明其在瘢痕组织中建立细胞间电连接方面具有重要作用。利用连接蛋白 43 敲除供体（bmpKO）生成的胎肝嵌合小鼠，进行光学标测以研究瘢痕的电生理特性。施加电流脉冲以引起电压变化。等电位图显示，与未损伤区域相比，在瘢痕处，从电极处的距离上电压下降的模式更为陡峭，表明电耦联减少。组织衰减常数定义为在瘢痕边缘处，电压达到振幅的 37%的距离，在 bmpCTL 组的瘢痕中为 0.48±0.04mm（n=11），在 bmpKO 组中降低了 37.5%（n=10）。这些数据共同表明，炎症细胞通过至少部分由连接蛋白 43 表达介导的偶联，对瘢痕的电生理学有显著贡献。
