Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes
Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes
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膜纳米管介导的心肌细胞和心成纤维细胞之间的长距离细胞间连接
DOI：
10.1093/cvr/cvr189
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发表时间：
2011-10-01
影响因子：
10.8
通讯作者：
Zhang, Youyi
中科院分区：
文献类型：
--
作者：
He, Kangmin;Shi, Xiaoli;Zhang, Youyi
心肌细胞（CM）和心脏成纤维细胞（FB）之间的细胞间相互作用在心脏的生理和病理生理中具有重要意义。了解这种相互作用对于开发有效的心脏病疗法非常重要。然而，直到最近，人们对这些相互作用知之甚少。我们的目的是探讨CM和FB之间的结构和功能连接是不同的gap junctions.Methods和results通过膜染料染色，我们观察到长，薄的膜纳米管结构，包含肌动蛋白和微管连接新生大鼠心室CM和FB。通过单粒子跟踪，我们观察到车辆之间的CM和FB膜纳米管内移动。通过双色染色、共聚焦成像和流式细胞术，我们观察了在共培养体系中CM和FB之间的线粒体交换。通过结合原子力显微镜（AFM）和共聚焦显微镜，我们观察了钙信号从AFM刺激的CM（或FB）到未刺激的FB（或CM）通过膜纳米管的传播。通过膜和细胞骨架染色，我们观察到类似的nanotubular结构在成年小鼠心脏tissue.Conclusions作为一种新型的CM FB通信，在体外和体内观察到的膜纳米管CM和FB之间的结构和功能连接长距离。
Aims Intercellular interactions between cardiomyocytes (CMs) and cardiofibroblasts (FBs) are important in the physiological and pathophysiological heart. Understanding such interactions is important for developing effective heart disease therapies. However, until recently, little has been known about these interactions. We aimed to investigate structural and functional connections between CMs and FBs that are distinct from gap junctions.Methods and results By membrane dye staining, we observed long, thin membrane nanotubular structures containing actin and microtubules that connected neonatal rat ventricular CMs and FBs. By single-particle tracking, we observed vehicles moving between CMs and FBs within the membrane nanotubes. By dual colour staining, confocal imaging and flow cytometry, we observed mitochondria exchange between CMs and FBs in a coculture system. By combined atomic force microscopy (AFM) and confocal microscopy, we observed calcium signal propagation from AFM-stimulated CM (or FB) to unstimulated FB (or CM) via membrane nanotubes. By membrane and cytoskeleton staining, we observed similar nanotubular structures in adult mouse heart tissue, which suggests their physiological relevance.Conclusions As a novel type of CM to FB communication, membrane nanotubes observed in vitro and in vivo provide structural and functional connectivity between CMs and FBs over long distances.