Authors: Shuoshuo Wang, Niranjana Natarajan, Anthony Zhu, Richard T Lee
Published: 2022-03-19
DOI: 10.1161/circ.144.suppl_1.11677
Source: Full article
The adult human heart is unable to regenerate after a major injury, while some vertebrates including neonatal mice heart possess substantial heart regeneration. In a previous multi-species transcriptome study, we identified Complement receptors C5aR1 and C3aR1 as evolutionarily conserved upregulated genes during the early phase of heart regeneration in multiple species. The complement system is a central mechanism in innate immunity, but its role in heart regeneration is unclear. After apical resection in neonatal mice, we administrated Cobra Venom Factor (CVF) to specifically deplete Complement, and the mice failed to regenerate the injured myocardium after three weeks. At 2 days after injury, the size of the sagittal area across post-traumatic granulation tissue was significantly reduced by 62.6% (n=5 each, p<0.05), suggesting that complement is necessary for myocardium regeneration through forming granulation tissue as a transient step. Furthermore, genetic deletion of the C3aR1 receptor (C3aR1-KO mice) phenotypically recapitulated the impaired myocardial regeneration observed in Complement-depleted animals. C3aR1 KO mice possessed significantly reduced number of Itgam