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Updated: Feb 15, 2026
07:48
Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
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Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration
Niranjana Natarajan1, Yamen Abbas1, Donald M Bryant1,2,3
1Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA (N.N., Y.A., D.M.B., A.U., L.H.C.-D., N.N.H., J.L.W., R.T.L.).
Circulation
|January 20, 2018
Summary
Investigating cardiac regeneration across species revealed that activating complement 5a receptor 1 promotes cardiomyocyte proliferation after heart injury, offering insights into successful heart repair mechanisms.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Comparative Genomics
Background:
- Adult mammals exhibit limited cardiac regeneration post-injury.
- Understanding conserved molecular pathways in animal models is key to unlocking mammalian heart repair.
- Transcriptomic analysis of early regeneration can illuminate evolutionarily conserved pathways.
Purpose of the Study:
- To conduct a cross-species transcriptomic screen for cardiac regeneration.
- To identify conserved molecular pathways involved in heart repair.
- To investigate the role of specific immune pathways in cardiomyocyte proliferation.
Main Methods:
- Comparative transcriptomic analysis of axolotl, neonatal mice, and zebrafish hearts post-injury.
- RNA sequencing at 12, 24, and 48 hours after apical resection (10-20% ventricular mass removal).
- Functional assessment of complement 5a receptor 1 (C5aR1) using inhibition and genetic deletion.
Main Results:
- Conserved upregulation of inflammatory and complement pathway genes, including complement receptors, was observed across species.
- Complement 5a receptor 1 (C5aR1) expression was induced in regenerating hearts.
- Inhibition or genetic deletion of C5aR1 significantly reduced cardiomyocyte proliferation following heart injury.
Conclusions:
- Activation of complement 5a receptor 1 is an evolutionarily conserved mechanism promoting cardiomyocyte proliferation after cardiac injury.
- Complement pathway activation represents a common pathway critical for successful heart regeneration.
- Targeting the complement pathway holds potential for enhancing cardiac repair.
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