ArticleCirculation research2015
Sympathetic Reinnervation Is Required for Mammalian Cardiac Regeneration.
Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 104 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Guidelines for experimental models of myocardial ischemia and infarction.American journal of physiology. Heart and circulatory physiology · 2018Guideline
- Neurovascular interactions in the ageing heart.Nature reviews. Cardiology · 2026Review
- Development and modeling of cardiac autonomic innervation.Nature cardiovascular research · 2025Review
- Cardiac Sympathetic Denervation Mitigated Ischemic Cardiomyopathy Progression in a Rat Model of Sleep Apnea.Journal of the American Heart Association · 2025Article
- Bioactive Inorganic Materials for Innervated Multi-Tissue Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Molecular and cellular neurocardiology in heart disease.The Journal of physiology · 2025Review
- Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.NPJ Regenerative medicine · 2025Review
- Macrophages producing chondroitin sulfate proteoglycan-4 induce neuro-cardiac junction impairment in Duchenne muscular dystrophy.The Journal of pathology · 2025Article
- Transition from fetal to postnatal state in the heart: Crosstalk between metabolism and regeneration.Development, growth & differentiation · 2024Review
- Heart regeneration from the whole-organism perspective to single-cell resolution.NPJ Regenerative medicine · 2024Review
- Murine neonatal cardiac regeneration depends on Insulin-like growth factor 1 receptor signaling.Scientific reports · 2024Article
- A modular platform to generate functional sympathetic neuron-innervated heart assembloids.Research square · 2024Article
- Regenerative loss in the animal kingdom as viewed from the mouse digit tip and heart.Developmental biology · 2024Review
- Article
- Targeting neuro-immune systems to achieve cardiac tissue repair following myocardial infarction: A review of therapeutic approaches from in-vivo preclinical to clinical studies.Pharmacology & therapeutics · 2023Review
- Angiogenesis: A critical determinant for cardiac regeneration.Molecular therapy. Nucleic acids · 2022Article
- The regenerative capacity of neonatal tissues.Development (Cambridge, England) · 2022Review
- LRP5 regulates cardiomyocyte proliferation and neonatal heart regeneration by the AKT/P21 pathway.Journal of cellular and molecular medicine · 2022Article
- Nerve regeneration in transplanted organs and tracer imaging studies: A review.Frontiers in bioengineering and biotechnology · 2022Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
rationaleAlthough 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.
objectiveTo test the hypothesis that reinnervation is required for innate neonatal cardiac regeneration. METHODS AND
resultsWe 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).
conclusionsThese 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 age-related influences and scar tissue.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.