Toggle Main Menu Toggle Search

Open Access padlockePrints

Senescent cardiomyocytes contribute to cardiac dysfunction following myocardial infarction

Lookup NU author(s): Dr Rachael Redgrave, Dr Emily Dookun, Laura Booth, Dr Maria Camacho EncinaORCiD, Dr Omowumi Folaranmi, Dr Simon Tual-Chalot, Dr Jason GillORCiD, Dr Andrew OwensORCiD, Professor Ioakim SpyridopoulosORCiD, Dr Joao Passos, Dr Gavin RichardsonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Myocardial infarction is a leading cause of morbidity and mortality. While reperfusion is now standard therapy, pathological remodelling leading to heart failure remains a clinical problem. Cellular senescence has been shown to contribute to disease pathophysiology and treatment with the senolytic navitoclax attenuates inflammation, reduces adverse myocardial remodelling and results in improved functional recovery. However, it remains unclear which senescent cell populations contribute to these processes. To identify whether senescent cardiomyocytes contribute to disease pathophysiology post-myocardial infarction, we established a transgenic model in which p16 (CDKN2A) expression was specifically knocked-out in the cardiomyocyte population. Following myocardial infarction, mice lacking cardiomyocyte p16 expression demonstrated no difference in cardiomyocyte hypertrophy but exhibited improved cardiac function and significantly reduced scar size in comparison to control animals. This data demonstrates that senescent cardiomyocytes participate in pathological myocardial remodelling. Importantly, inhibition of cardiomyocyte senescence led to reduced senescence-associated inflammation and decreased senescence-associated markers within other myocardial lineages, consistent with the hypothesis that cardiomyocytes promote pathological remodelling by spreading senescence to other cell-types. Collectively this study presents the demonstration that senescent cardiomyocytes are major contributors to myocardial remodelling and dysfunction following a myocardial infarction. Therefore, to maximise the potential for clinical translation, it is important to further understand the mechanisms underlying cardiomyocyte senescence and how to optimise senolytic strategies to target this cell lineage.

Publication metadata

Author(s): Redgrave R, Dookun E, Booth LK, Camacho Encina M, Folaranmi O, Tual-Chalot S, Gill JH, Owens WA, Spyridopoulos I, Passos JF, Richardson GD

Publication type: Article

Publication status: Published

Journal: npj Aging

Year: 2023

Volume: 9

Print publication date: 14/06/2023

Online publication date: 14/06/2023

Acceptance date: 01/06/2023

Date deposited: 20/06/2023

ISSN (electronic): 2731-6068

Publisher: Nature


DOI: 10.1038/s41514-023-00113-5

PubMed id: 37316516


Altmetrics provided by Altmetric