ArticleCirculation2018
Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration.
Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis 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
49 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Single-cell transcriptomics and machine learning identify RNF144B and C5AR1 as immune-related molecular signatures and therapeutic targets in myocardial infarction.Genes & genomics · 2026Article
- Epicardial Complement C3 Activation in Neonatal Cardiac Regeneration.Circulation · 2026Article
- The α-Gal Epitope (Galα1-3Galβ1-4GlcNAc) as Therapeutic Agent in Cancer Immunotherapy, Vaccine Effectiveness Amplification and Injured Tissue Regeneration.International journal of molecular sciences · 2026Review
- Lessons of Macrophage-Associated Heart Regeneration in Fish, Amphibians, and Neonatal Mice, Applied to Adult Mice: A Perspective on α-Gal Nanoparticles.International journal of molecular sciences · 2026Review
- Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches.International journal of molecular sciences · 2026Review
- Functional Roles of the Complement Immune System in Cardiac Inflammation and Hypertrophy.International journal of molecular sciences · 2025Review
- Cardiac Repair after Myocardial Infarction is Controlled by a Complement C5a Receptor 1-Driven Signaling Cascade.Thrombosis and haemostasis · 2025Article
- A cellular triad for linking cardiac niche to regeneration.Cell regeneration (London, England) · 2024Article
- Transition from fetal to postnatal state in the heart: Crosstalk between metabolism and regeneration.Development, growth & differentiation · 2024Review
- Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions.Nature communications · 2024Article
- Regeneration in Mice of Injured Skin, Heart, and Spinal Cord by α-Gal Nanoparticles Recapitulates Regeneration in Amphibians.Nanomaterials (Basel, Switzerland) · 2024Review
- YAP induces a neonatal-like pro-renewal niche in the adult heart.Nature cardiovascular research · 2024Article
- Complement System Inhibitory Drugs in a Zebrafish (International journal of molecular sciences · 2023Article
- Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart-Part II: Molecular Mechanisms of Cardiac Regeneration.Journal of cardiovascular development and disease · 2023Review
- A modified apical resection model with high accuracy and reproducibility in neonatal mouse and rat hearts.NPJ Regenerative medicine · 2023Article
- Molecular Actors of Inflammation and Their Signaling Pathways: Mechanistic Insights from Zebrafish.Biology · 2023Review
- Antibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies.Frontiers in molecular biosciences · 2023Review
- Surviving without oxygen involves major tissue specific changes in the proteome of crucian carp (PeerJ · 2023Article
- C1q and the classical complement cascade in geographic atrophy secondary to age-related macular degeneration.International journal of retina and vitreous · 2022Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
backgroundDefining conserved molecular pathways in animal models of successful cardiac regeneration could yield insight into why adult mammals have inadequate cardiac regeneration after injury. Insight into the transcriptomic landscape of early cardiac regeneration from model organisms will shed light on evolutionarily conserved pathways in successful cardiac regeneration.
methodsHere we describe a cross-species transcriptomic screen in 3 model organisms for cardiac regeneration: axolotl, neonatal mice, and zebrafish. Apical resection to remove ≈10% to 20% of ventricular mass was carried out in these model organisms. RNA-sequencing analysis was performed on the hearts harvested at 3 time points: 12, 24, and 48 hours after resection. Sham surgery was used as internal control.
resultsGenes associated with inflammatory processes were found to be upregulated in a conserved manner. Complement receptors (activated by complement components, part of the innate immune system) were found to be highly upregulated in all 3 species. This approach revealed induction of gene expression for complement 5a receptor 1 in the regenerating hearts of zebrafish, axolotls, and mice. Inhibition of complement 5a receptor 1 significantly attenuated the cardiomyocyte proliferative response to heart injury in all 3 species. Furthermore, after left ventricular apical resection, the cardiomyocyte proliferative response was diminished in mice with genetic deletion of complement 5a receptor 1.
conclusionsThese data reveal that activation of complement 5a receptor 1 mediates an evolutionarily conserved response that promotes cardiomyocyte proliferation after cardiac injury and identify complement pathway activation as a common pathway of successful heart regeneration.
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