title: Long-distance intercellular connectivity between cardiomyocytes and cardiofibroblasts mediated by membrane nanotubes.
abstract: OBJECTIVE
  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.
  
  
  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.
authors: 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.
authors: Kangmin
authors: K
authors: He
authors: Xiaoli
authors: X
authors: Shi
authors: Xuejie
authors: X
authors: Zhang
authors: Song
authors: S
authors: Dang
authors: Xiaowei
authors: X
authors: Ma
authors: Fei
authors: F
authors: Liu
authors: Ming
authors: M
authors: Xu
authors: Zhizhen
authors: Z
authors: Lv
authors: Dong
authors: D
authors: Han
authors: Xiaohong
authors: X
authors: Fang
authors: Youyi
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling; D002450:Cell Communication; D005347:Fibroblasts / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000502:physiology*; D043942:Nanotubes; D051381:Rats; D017207:Rats, Sprague-Dawley