論文

査読有り
2017年7月

Quantification of sympathetic hyperinnervation and denervation after myocardial infarction by three-dimensional assessment of the cardiac sympathetic network in cleared transparent murine hearts

PLOS ONE
  • Teruki Yokoyama
  • ,
  • Jong-Kook Lee
  • ,
  • Keiko Miwa
  • ,
  • Tobias Opthof
  • ,
  • Satoki Tomoyama
  • ,
  • Hiroyuki Nakanishi
  • ,
  • Akira Yoshida
  • ,
  • Haruyo Yasui
  • ,
  • Tadatsune Iida
  • ,
  • Shigeru Miyagawa
  • ,
  • Shigeo Okabe
  • ,
  • Yoshiki Sawa
  • ,
  • Yasushi Sakata
  • ,
  • Issei Komuro

12
7
開始ページ
e0182072
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0182072
出版者・発行元
PUBLIC LIBRARY SCIENCE

BackgroundThe sympathetic nervous system is critical in maintaining the normal physiological function of the heart. Its dysfunction in pathological states may exacerbate the substrate for arrhythmias. Obviously, knowledge of its three-dimensional (3D) structure is important, however, it has been revealed by conventional methods only to a limited extent. In this study, a new method of tissue clearance in combination with immunostaining unravels the 3D structure of the sympathetic cardiac network as well as its changes after myocardial infarction.Methods and resultsHearts isolated from adult male mice were optically cleared using the CUBIC-perfusion protocol. After making the hearts transparent, sympathetic nerves and coronary vessels were immunofluorescently labeled, and then images were acquired. The spatial distribution of sympathetic nerves was visualized not only along the epicardial surface, but also transmurally. They were distributed over the epicardial surface and penetrated into the myocardium to twist around coronary vessels, but also independent from the coronary vasculature. At 2 weeks after myocardial infarction, we were able to quantify both denervation distal from the site of infarction and nerve sprouting (hyperinnervation) at the ischemic border zone of the hearts in a 3D manner. The nerve density at the ischemic border zone was more than doubled in hearts with myocardial infarction compared to intact mice hearts (3D analyses; n = 5, p<0.05).ConclusionsThere is both sympathetic hyperinnervation and denervation after myocardial infarction. Both can be visualized and quantified by a new imaging technique in transparent hearts and thereby become a useful tool in elucidating the role of the sympathetic nervous system in arrhythmias associated with myocardial infarction.

Web of Science ® 被引用回数 : 8

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0182072
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28753665
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000406579300046&DestApp=WOS_CPL

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