論文

査読有り
2021年12月

Non-neuronal cardiac acetylcholine system playing indispensable roles in cardiac homeostasis confers resiliency to the heart

The Journal of Physiological Sciences
  • Shino Oikawa
  • ,
  • Yuko Kai
  • ,
  • Asuka Mano
  • ,
  • Hisayuki Ohata
  • ,
  • Atsushi Kurabayashi
  • ,
  • Masayuki Tsuda
  • ,
  • Yoshihiko Kakinuma

71
1
開始ページ
2
終了ページ
2
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1186/s12576-020-00787-6
出版者・発行元
Springer Science and Business Media LLC

<title>Abstract</title><sec>
<title>Background</title>
We previously established that the non-neuronal cardiac cholinergic system (NNCCS) is equipped with cardiomyocytes synthesizes acetylcholine (ACh), which is an indispensable endogenous system, sustaining cardiac homeostasis and regulating an inflammatory status, by transgenic mice overexpressing choline acetyltransferase (ChAT) gene in the heart. However, whole body biological significances of NNCCS remain to be fully elucidated.


</sec><sec>
<title>Methods and results</title>
To consolidate the features, we developed heart-specific ChAT knockdown (ChATKD) mice using 3 ChAT-specific siRNAs. The mice developed cardiac dysfunction. Factors causing it included the downregulation of cardiac glucose metabolism along with decreased signal transduction of Akt/HIF-1alpha/GLUT4, leading to poor glucose utilization, impairment of glycolytic metabolites entering the tricarboxylic (TCA) cycle, the upregulation of reactive oxygen species (ROS) production with an attenuated scavenging potency, and the downregulated nitric oxide (NO) production via NOS1. ChATKD mice revealed a decreased vagus nerve activity, accelerated aggression, more accentuated blood basal corticosterone levels with depression-like phenotypes, several features of which were accompanied by cardiac dysfunction.


</sec><sec>
<title>Conclusion</title>
The NNCCS plays a crucial role in cardiac homeostasis by regulating the glucose metabolism, ROS synthesis, NO levels, and the cardiac vagus nerve activity. Thus, the NNCCS is suggested a fundamentally crucial system of the heart.


</sec>

リンク情報
DOI
https://doi.org/10.1186/s12576-020-00787-6
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/33461483
URL
http://link.springer.com/content/pdf/10.1186/s12576-020-00787-6.pdf
URL
http://link.springer.com/article/10.1186/s12576-020-00787-6/fulltext.html
ID情報
  • DOI : 10.1186/s12576-020-00787-6
  • ISSN : 1880-6546
  • eISSN : 1880-6562
  • PubMed ID : 33461483

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