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Article Dans Une Revue Aging Cell Année : 2024

Identification of Prominin‐2 as a new player of cardiomyocyte senescence in the aging heart

Résumé

The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell‐specific markers. Cardiomyocytes undergo post‐mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53‐dependent pathway in stress‐induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin‐treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell‐type specific senescence in age‐associated cardiac diseases.
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hal-04618754 , version 1 (20-06-2024)

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Damien Maggiorani, Yohan Santin, Karina Formoso, E. Drapé, Hélène Martini, et al.. Identification of Prominin‐2 as a new player of cardiomyocyte senescence in the aging heart. Aging Cell, 2024, 17, pp.e14204. ⟨10.1111/acel.14204⟩. ⟨hal-04618754⟩
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