ArticlePloS one2014
Recombinant neuregulin 1 does not activate cardiomyocyte DNA synthesis in normal or infarcted adult mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Cardiac Regeneration: New Insights Into the Frontier of Ischemic Heart Failure Therapy.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Review
- Cell-free strategies for cardiomyocyte proliferation and heart repair.Pharmacological reports : PR · 2026Review
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.Journal of molecular and cellular cardiology · 2025Article
- Small-molecule-induced ERBB4 activation to treat heart failure.Nature communications · 2025Article
- Epigenetic determinants and non-myocardial signaling pathways contributing to heart growth and regeneration.Pharmacology & therapeutics · 2024Review
- Effects and mechanisms of the myocardial microenvironment on cardiomyocyte proliferation and regeneration.Frontiers in cell and developmental biology · 2024Review
- Musings on intrinsic cardiomyocyte cell cycle activity and myocardial regeneration.Journal of molecular and cellular cardiology · 2023Review
- Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.Circulation · 2023Article
- The regenerative capacity of neonatal tissues.Development (Cambridge, England) · 2022Review
- Innate Mechanisms of Heart Regeneration.Cold Spring Harbor perspectives in biology · 2021Review
- Molecular regulation of myocardial proliferation and regeneration.Cell regeneration (London, England) · 2021Review
- Mechanism-Based Cardiac Regeneration Strategies in Mammals.Frontiers in cell and developmental biology · 2021Review
- Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration.Basic research in cardiology · 2020Review
- Function Follows Form - A Review of Cardiac Cell Therapy.Circulation journal : official journal of the Japanese Circulation Society · 2019Review
- The small molecule Chicago Sky Blue promotes heart repair following myocardial infarction in mice.JCI insight · 2019Article
- Cardiomyocyte cell cycle dynamics and proliferation revealed through cardiac-specific transgenesis of fluorescent ubiquitinated cell cycle indicator (FUCCI).Journal of molecular and cellular cardiology · 2019Article
- Three in a Box: Understanding Cardiomyocyte, Fibroblast, and Innate Immune Cell Interactions to Orchestrate Cardiac Repair Processes.Frontiers in cardiovascular medicine · 2019Review
- Therapeutic approaches for cardiac regeneration and repair.Nature reviews. Cardiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesNeuregulin 1 signaling plays an important role in cardiac trabecular development, and in sustaining functional integrity in adult hearts. Treatment with neuregulin 1 enhances adult cardiomyocyte differentiation, survival and/or function in vitro and in vivo. It has also been suggested that recombinant neuregulin 1β1 (NRG1β1) induces cardiomyocyte proliferation in normal and injured adult hearts. Here we further explore the impact of neuregulin 1 signaling on adult cardiomyocyte cell cycle activity. METHODS AND
resultsAdult mice were subjected to 9 consecutive daily injections of recombinant NRG1β1 or vehicle, and cardiomyocyte DNA synthesis was quantitated via bromodeoxyuridine (BrdU) incorporation, which was delivered using mini-osmotic pumps over the entire duration of NRG1β1 treatment. NRG1β1 treatment inhibited baseline rates of cardiomyocyte DNA synthesis in normal mice (cardiomyocyte labelling index: 0.019±0.005% vs. 0.003±0.001%, saline vs. NRG1β1, P<0.05). Acute NRG1β1 treatment did result in activation of Erk1/2 and cardiac myosin regulatory light chain (down-stream mediators of neuregulin signalling), as well as activation of DNA synthesis in non-cardiomyocytes, validating the biological activity of the recombinant protein. In other studies, mice were subjected to permanent coronary artery occlusion, and cardiomyocyte DNA synthesis was monitored via tritiated thymidine incorporation which was delivered as a single injection 7 days post-infarction. Daily NRG1β1 treatment had no impact on cardiomyocyte DNA synthesis in the infarcted myocardium (cardiomyocyte labelling index: 0.039±0.011% vs. 0.027±0.021%, saline vs. NRG1β1, P>0.05). SUMMARY: These data indicate that NRG1β1 treatment does not increase cardiomyocyte DNA synthesis (and consequently does not increase the rate of cardiomyocyte renewal) in normal or infarcted adult mouse hearts. Thus, any improvement in cardiac structure and function observed following neuregulin treatment of injured hearts likely occurs independently of overt myocardial regeneration.
Indexed as
Identifiers
What OpenQuestion holds
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.