Key result
Myocardial infarction did not significantly increase bona fide cardiomyocyte proliferation compared to sham in adult mice, although Ki67+ cycling cells increased in the infarct border zone.
Why the study?
Previous studies suggested cardiomyocyte proliferation increases after injury, but results in adult mammalian hearts remain controversial partly due to differing methodologies.
Does myocardial infarction improve cardiomyocyte proliferation in adult mice?
Meta-Analysis
Does myocardial infarction improve cardiomyocyte proliferation in adult mice?
Mean Difference: -0.04 (95% CI -0.27–0.19)
Myocardial infarction does not provide overwhelming evidence of stimulating bona fide cardiomyocyte proliferation in the adult mouse heart, despite localized increases in cell cycle markers.
MI does not induce bona fide cardiomyocyte proliferation in adult mice; challenges regeneration hypotheses and refines research endpoints.
The proliferation capacity of adult cardiomyocytes is very limited in the normal adult mammalian heart. Previous studies implied that cardiomyocyte proliferation increases after injury stimulation, but the result is controversial partly due to different methodologies. We aim to evaluate whether myocardial infarction (MI) stimulates cardiomyocyte proliferation in adult mice. A comprehensive literature search was conducted through PubMed/Medline, Embase, and Web of Science databases from 1 January 2000 to 21 December 2023. The SYRCLE’s Risk of Bias tool for animal experiments was used to evaluate the quality of the literature by two independent reviewers. Twenty-six studies with cell cycle indicators (Ki67+, PH3+, BrdU/EdU+, and AurkB+) to evaluate cycling cardiomyocytes were collected for a meta-analysis. Another 10 studies with genetic reporter/tracing systems to evaluate cardiomyocyte proliferation were collected for a systematic review. Evaluating cardiomyocyte proliferation by immunostaining of the cell cycle indicators on heart tissue, the meta-analysis showed that differences of Ki67+, PH3+, and BrdU/EdU+ cycling cardiomyocytes between MI and Sham groups were not statistically significant. In the post-MI heart, the percentages of PH3+, BrdU/EdU+, and AurkB+ cardiomyocytes were not significantly different between the infarct border zone and remote zone. The percentage of Ki67+ cardiomyocytes in the infarct border zone was statistically higher than that in the remote zone. Most of the studies (6 out of 10) using genetic reporter/tracing mouse systems showed that the difference in cardiomyocyte proliferation between MI and Sham groups was not statistically significant. Among the other 4 studies, at least 3 studies could not demonstrate that MI stimulates bona fide cardiomyocyte proliferation because of methodological shortages. MI injury increases Ki67+ cycling adult mouse cardiomyocytes in infarct border zone. Very little overwhelming evidence shows that MI stimulates bona fide proliferation in the adult heart.
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Liu et al. (2024) conducted a meta-analysis in Myocardial infarction. Myocardial infarction vs. Sham operation was evaluated on Percentage of Ki67+ cycling cardiomyocytes (MD -0.04%, 95% CI -0.27 to 0.19). Myocardial infarction did not significantly increase bona fide cardiomyocyte proliferation compared to sham in adult mice, although Ki67+ cycling cells increased in the infarct border zone.
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