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
Original language | English (US) |
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Pages (from-to) | 990-994 |
Number of pages | 5 |
Journal | Circulation Research |
Volume | 117 |
Issue number | 12 |
DOIs | |
State | Published - 2015 |
Externally published | Yes |
Keywords
- Mice
- Myocardium
- Regeneration
- Sympathectomy
- Sympathetic nervous system
- Transgenic
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine