A Meta-analysis and Systematic Review of Myocardial Infarction-induced Cardiomyocyte Proliferation in Adult Mouse Heart

Overview

Journal BMC Med

Publisher Biomed Central

Specialty General Medicine

Date 2024 Dec 30

PMID 39736615

Authors

Ya Liu

Lingyan Liu

Pengcheng Zhuang

Jiamin Zou

Xiaokang Chen

Hao Wu

Bingjun Lu

Wei Eric Wang

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

References

Senyo S, Steinhauser M, Pizzimenti C, Yang V, Cai L, Wang M . Mammalian heart renewal by pre-existing cardiomyocytes. Nature. 2012; 493(7432):433-6. PMC: 3548046. DOI: 10.1038/nature11682. View

Reuter S, Soonpaa M, Field D, Simpson E, Rubart-von der Lohe M, Lee H . Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation. Circulation. 2022; 147(2):142-153. PMC: 9839600. DOI: 10.1161/CIRCULATIONAHA.122.061130. View

Fu W, Liao Q, Li L, Shi Y, Zeng A, Zeng C . An Aurora Kinase B-Based Mouse System to Efficiently Identify and Analyze Proliferating Cardiomyocytes. Front Cell Dev Biol. 2020; 8:570252. PMC: 7575716. DOI: 10.3389/fcell.2020.570252. View

Avolio E, Meloni M, Spencer H, Riu F, Katare R, Mangialardi G . Combined intramyocardial delivery of human pericytes and cardiac stem cells additively improves the healing of mouse infarcted hearts through stimulation of vascular and muscular repair. Circ Res. 2015; 116(10):e81-94. DOI: 10.1161/CIRCRESAHA.115.306146. View

Ahmad F, Lal H, Zhou J, Vagnozzi R, Yu J, Shang X . Cardiomyocyte-specific deletion of Gsk3α mitigates post-myocardial infarction remodeling, contractile dysfunction, and heart failure. J Am Coll Cardiol. 2014; 64(7):696-706. PMC: 4142642. DOI: 10.1016/j.jacc.2014.04.068. View

Ma W, Song R, Xu B, Xu Y, Wang X, Sun H . Melatonin promotes cardiomyocyte proliferation and heart repair in mice with myocardial infarction via miR-143-3p/Yap/Ctnnd1 signaling pathway. Acta Pharmacol Sin. 2020; 42(6):921-931. PMC: 8149448. DOI: 10.1038/s41401-020-0495-2. View

Broughton K, Sussman M . Adult Cardiomyocyte Cell Cycle Detour: Off-ramp to Quiescent Destinations. Trends Endocrinol Metab. 2019; 30(8):557-567. PMC: 6703820. DOI: 10.1016/j.tem.2019.05.006. View

Wang X, Wan T, Lauth A, Purdy A, Kulik K, Patterson M . Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction. J Mol Cell Cardiol. 2021; 163:9-19. PMC: 8816866. DOI: 10.1016/j.yjmcc.2021.09.012. View

Gao X, Li H, Zhang W, Wang X, Sun H, Cao Y . Photobiomodulation Drives MiR-136-5p Expression to Promote Injury Repair after Myocardial Infarction. Int J Biol Sci. 2022; 18(7):2980-2993. PMC: 9066112. DOI: 10.7150/ijbs.71440. View

10.

Gong R, Wang X, Li H, Liu S, Jiang Z, Zhao Y . Loss of mA methyltransferase METTL3 promotes heart regeneration and repair after myocardial injury. Pharmacol Res. 2021; 174:105845. DOI: 10.1016/j.phrs.2021.105845. View

11.

Mohamed T, Ang Y, Radzinsky E, Zhou P, Huang Y, Elfenbein A . Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration. Cell. 2018; 173(1):104-116.e12. PMC: 5973786. DOI: 10.1016/j.cell.2018.02.014. View

12.

Wang W, Li L, Xia X, Fu W, Liao Q, Lan C . Dedifferentiation, Proliferation, and Redifferentiation of Adult Mammalian Cardiomyocytes After Ischemic Injury. Circulation. 2017; 136(9):834-848. PMC: 5575972. DOI: 10.1161/CIRCULATIONAHA.116.024307. View

13.

Magadum A, Ding Y, He L, Kim T, Vasudevarao M, Long Q . Live cell screening platform identifies PPARδ as a regulator of cardiomyocyte proliferation and cardiac repair. Cell Res. 2017; 27(8):1002-1019. PMC: 5539351. DOI: 10.1038/cr.2017.84. View

14.

Turner R, Davey J, Clarke M, Thompson S, Higgins J . Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews. Int J Epidemiol. 2012; 41(3):818-27. PMC: 3396310. DOI: 10.1093/ije/dys041. View

15.

Page M, McKenzie J, Bossuyt P, Boutron I, Hoffmann T, Mulrow C . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372:n71. PMC: 8005924. DOI: 10.1136/bmj.n71. View

16.

Liu X, Pu W, He L, Li Y, Zhao H, Li Y . Cell proliferation fate mapping reveals regional cardiomyocyte cell-cycle activity in subendocardial muscle of left ventricle. Nat Commun. 2021; 12(1):5784. PMC: 8486850. DOI: 10.1038/s41467-021-25933-5. View

17.

Lima Correa B, El Harane N, Desgres M, Perotto M, Alayrac P, Guillas C . Extracellular vesicles fail to trigger the generation of new cardiomyocytes in chronically infarcted hearts. Theranostics. 2021; 11(20):10114-10124. PMC: 8581432. DOI: 10.7150/thno.62304. View

18.

Kretzschmar K, Post Y, Bannier-Helaouet M, Mattiotti A, Drost J, Basak O . Profiling proliferative cells and their progeny in damaged murine hearts. Proc Natl Acad Sci U S A. 2018; 115(52):E12245-E12254. PMC: 6310797. DOI: 10.1073/pnas.1805829115. View

19.

Xie Y, Ibrahim A, Cheng K, Wu Z, Liang W, Malliaras K . Importance of cell-cell contact in the therapeutic benefits of cardiosphere-derived cells. Stem Cells. 2014; 32(9):2397-406. PMC: 4138271. DOI: 10.1002/stem.1736. View

20.

Yan W, Lin C, Guo Y, Chen Y, Du Y, Lau W . N-Cadherin Overexpression Mobilizes the Protective Effects of Mesenchymal Stromal Cells Against Ischemic Heart Injury Through a β-Catenin-Dependent Manner. Circ Res. 2020; 126(7):857-874. DOI: 10.1161/CIRCRESAHA.119.315806. View