CD47 blockade reduces doxorubicin-induced cardiac aging in male mice

Inhibiting CD47 lessens heart dysfunction and blunts cellular senescence caused by the chemotherapy drug doxorubicin.

Figure 1. CD47 expression in the aged rat hearts from the GEO database and quantification by q‐PCR and western‐blotting assays in aged mouse hearts.CD47 expression in the aged rat hearts from the GEO database and quantification by q‐PCR and western‐blotting assays in aged mouse hearts.Yan et al. · CC BY

Physiological Reports3 Oct 2026, 01:04 BST

In male mice and cultured AC16 cardiomyocytes, researchers examined how CD47 regulates chemotherapy-induced cardiac aging. Initial bioinformatic analyses revealed that CD47 increases in aged hearts. The team then treated mice with doxorubicin, which raised CD47 expression alongside senescence markers p53, p16, and p21 in heart tissue. In AC16 cells, doxorubicin similarly boosted CD47 levels, p16, p21, and senescence-associated beta-galactosidase activity. Blocking CD47 with a specific antibody reduced cardiomyocyte senescence both in vitro and in vivo. Furthermore, CD47 inhibition improved doxorubicin-induced cardiac dysfunction in the animals.

Why it matters

Anticancer therapies frequently accelerate cardiac aging and functional decline. Identifying CD47 as a mediator of this process reveals a mechanistic link between therapy-induced stress and tissue senescence.

Caveats

The findings rely on cultured cells and male mice rather than human patients. Further work is needed to determine whether these effects translate across sexes and into clinical settings.