Institute of Vascular Medicine of Third Hospital, Ministry of Education Key Lab of Molecular Cardiovascular Sciences, Ministry of Health Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides and Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100191, PR China.
Cardiovasc Res. 2011 Oct 1;92(1):39-47. doi: 10.1093/cvr/cvr189. Epub 2011 Jun 30.
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.
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.
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.
心肌细胞 (CMs) 和心成纤维细胞 (FBs) 之间的细胞间相互作用在心脏的生理和病理生理中很重要。了解这些相互作用对于开发有效的心脏疾病疗法很重要。然而，直到最近，人们对这些相互作用知之甚少。我们旨在研究 CMs 和 FBs 之间除了间隙连接之外的结构和功能连接。
通过细胞膜染料染色，我们观察到含有肌动蛋白和微管的长而细的细胞膜纳米管状结构，将新生大鼠心室 CMs 和 FBs 连接起来。通过单颗粒跟踪，我们观察到在细胞膜纳米管内，载体在 CMs 和 FBs 之间移动。通过双色染色、共聚焦成像和流式细胞术，我们观察到在共培养系统中 CMs 和 FBs 之间的线粒体交换。通过原子力显微镜 (AFM) 和共聚焦显微镜的组合，我们观察到通过细胞膜纳米管从 AFM 刺激的 CM (或 FB) 到未刺激的 FB (或 CM) 的钙信号传播。通过细胞膜和细胞骨架染色，我们观察到在成年小鼠心脏组织中存在类似的纳米管状结构，这表明它们具有生理相关性。
作为一种新型的 CM 到 FB 通讯方式，在体外和体内观察到的细胞膜纳米管提供了 CMs 和 FBs 之间的长距离结构和功能连接。
