E2F7/8 is involved in cardiomyocyte polyploidy but does not affect myocardial reperfusion injury recovery

• Published in: Cardiovascular research Vol. 118; no. Supplement_1
• Main Authors: Fang, J, Van Der Geest, JSA, Yao, B, Yang, Q, Chirico, N, Brans, MA, Roefs, MT, Vader, P, De Jager, SCA, De Bruin, A, Vink, A, Van Mil, A, Schiffelers, RM, Lei, Z, Sluijter, JPG
• Format: Journal Article
• Language: English
• Published: Oxford University Press 10.06.2022
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/cvac066.061

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): CSC fellowship Background Polyploidy cells consist of more than two complete sets of homologous chromosomes. Although a characteristic feature of cardiomyocytes and observed in all mammalian species, its molecular mechanism and biological functions are still unknown. Cardiomyocytes polyploidy in rodents occurs mainly through incomplete cytokinesis and increases with age. Studies have demonstrated that E2F7/8 transcription factors are key regulators of polyploidy in the liver and pancreas, however, it remains unclear if E2F7/8 control the generation of polyploidy cardiomyocytes and what the functional consequence is post-myocardial infarction (MI). Methods By using a tamoxifen inducible Cre/LoxP approach in new-born mice, we deleted E2F7/8 transcription factors ubiquitously and evaluated the biological significance of postnatal E2F7/8 loss. Mice underwent myocardial ischemia reperfusion injury (IRI) and heart function was assessed by 4D-echocardiography. Cardiomyocyte nucleus polyploidy was measured by FACS and microscope. Results Deficiency of E2F7/8 significantly suppress cardiomyocyte mononucleated and multinucleated polyploidy, as well as dramatically decreased hepatocytes polyploidy. E2F7/8 defect also led to a decrease in cardiac stress related marker lever such as ANP, BNP, MMP2, β-MHC/α-MHC and an increase in CD31 expression level. Surprisingly, E2F7/8 deletion did not have impact on cardiac function and dimensions post-IRI. Conclusion In summary, we identified that E2F7/8 activity is involved in the cellular polyploidy in the heart but did not affect myocardial function after myocardial injury.