Liu Ya, Liu Lingyan, Zhuang Pengcheng, Zou Jiamin, Chen Xiaokang, Wu Hao, Lu Bingjun, Wang Wei Eric
Department of Geriatrics, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Street, Chongqing, 400038, China.
BMC Med. 2024 Dec 31;22(1):603. doi: 10.1186/s12916-024-03822-0.
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.
在正常成年哺乳动物心脏中，成年心肌细胞的增殖能力非常有限。先前的研究表明，损伤刺激后心肌细胞增殖会增加，但由于方法不同，结果存在争议。我们旨在评估心肌梗死（MI）是否会刺激成年小鼠心肌细胞增殖。
通过PubMed/Medline、Embase和Web of Science数据库对2000年1月1日至2023年12月21日的文献进行全面检索。使用SYRCLE动物实验偏倚风险工具由两名独立评审员评估文献质量。收集了26项使用细胞周期指标（Ki67、PH3、BrdU/EdU和AurkB）评估循环心肌细胞的研究进行荟萃分析。另外收集了10项使用基因报告/追踪系统评估心肌细胞增殖的研究进行系统评价。
通过对心脏组织进行细胞周期指标免疫染色评估心肌细胞增殖，荟萃分析显示MI组和假手术组之间Ki67、PH3和BrdU/EdU循环心肌细胞的差异无统计学意义。在心肌梗死后的心脏中，梗死边缘区和远隔区的PH3、BrdU/EdU和AurkB心肌细胞百分比无显著差异。梗死边缘区Ki67心肌细胞百分比在统计学上高于远隔区。大多数使用基因报告/追踪小鼠系统的研究（10项中的6项）显示MI组和假手术组之间心肌细胞增殖差异无统计学意义。在其他4项研究中，至少有3项研究由于方法学缺陷未能证明MI刺激了真正的心肌细胞增殖。
MI损伤增加了梗死边缘区成年小鼠Ki67循环心肌细胞。几乎没有压倒性证据表明MI刺激了成年心脏中的真正增殖。
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