Sympathetic reinnervation is required for mammalian cardiac regeneration

Ian A. White, Julie Gordon, Wayne Balkan, Joshua M. Hare

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Rationale: Although mammalian cardiac regeneration can occur in the neonatal period, the factors involved in this process remain to be established. Because tissue and limb regeneration require concurrent reinnervation by the peripheral nervous system, we hypothesized that cardiac regeneration also requires reinnervation. Objective: To test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. Methods and Results: We crossed a Wnt1-Cre transgenic mouse with a double-tandem Tomato reporter strain to identify neural crest-derived cell lineages including the peripheral autonomic nerves in the heart. This approach facilitated the precise visualization of subepicardial autonomic nerves in the ventricles using whole mount epifluorescence microscopy. After resection of the left ventricular apex in 2-day-old neonatal mice, sympathetic nerve structures, which envelop the heart under normal conditions, exhibited robust regrowth into the regenerating myocardium. Chemical sympathectomy inhibited sympathetic regrowth and subsequent cardiac regeneration after apical resection significantly (scar size as cross-sectional percentage of viable left ventricular myocardium, n=9; 0.87%±1.4% versus n=6; 14.05±4.4%; P<0.01). Conclusions: These findings demonstrate that the profound regenerative capacity of the neonatal mammalian heart requires sympathetic innervation. As such, these data offer significant insights into an underlying basis for inadequate adult regeneration after myocardial infarction, a situation where nerve growth is hindered by agerelated influences and scar tissue.

Original languageEnglish (US)
Pages (from-to)990-994
Number of pages5
JournalCirculation research
Volume117
Issue number12
DOIs
StatePublished - 2015

Keywords

  • Mice
  • Myocardium
  • Regeneration
  • Sympathectomy
  • Sympathetic nervous system
  • Transgenic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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