Cell Cycle Withdrawal Limit the Regenerative Potential of Neonatal Cardiomyocytes

Yan, Huili and Rao, Xiyun and Wang, Rui and Zhu, Shichao and Liu, Renjing and Zheng, Xiangjian (2021) Cell Cycle Withdrawal Limit the Regenerative Potential of Neonatal Cardiomyocytes. Cardiovascular Engineering and Technology, 12 (5). pp.475-484. ISSN 1869-408X

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Link to published document: http://doi.org/10.1007/s13239-021-00551-w


PURPOSE: The neonatal mouse possesses a transient capacity for cardiac regeneration during the first few days of life. The regenerative response of neonatal mouse is primarily mediated by pre-existing cardiomyocyte (CM) proliferation, which has been identified as the primary source of myocardial regeneration. Postnatal 4-day-old (P4) mouse CMs appear to undergo a rapid transition from hyperplastic to hypertrophic growth and binucleation. By 7 days following birth this regenerative potential is lost which coincidently correspond with CM cell cycle arrest and binucleation. CCM2-like (Ccm2l) plays pivotal roles in cardiovascular development and cardiac growth, indicating a potential function in heart regeneration postnatally. The aim of this study was to determine the cardiac regeneration ability of P4 neonatal mouse using a novel and more reproducible injury model and to determine whether Ccm2l has any functional roles in heart repair following ischemic injury. METHODS: We performed a modified left anterior descending artery (LAD) ligation procedure on P4 mice to examine cardiac regenerative responses at different time points. Additionally, we generated an endothelial-specific Ccm2l gain-of-function transgenic mouse to determine the role of Ccm2l in neonatal cardiac regeneration. RESULTS: We found that the P4 mouse heart harbor a robust regenerative response after injury that was through the proliferation of pre-existing CMs but cardiac hypertrophy and subsequent remodeling was still evident 60 days after LAD ligation. Furthermore, we show that endothelial-specific overexpression of Ccm2l does not promote CM proliferation and heart repair after LAD ligation. CONCLUSION: The neonatal heart at P4 harbors a robust but incomplete capacity for cardiac regeneration. Endothelial overexpression of Ccm2l has no effect on cardiac regeneration.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 10 Dec 2021 04:10
Last Modified: 10 Dec 2021 04:10
URI: http://eprints.victorchang.edu.au/id/eprint/1183

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