Reactive fibrosis precedes doxorubicin-induced heart failure through sterile inflammation.

ABSTRACT:

Aims

Doxorubicin (DOX)-induced heart failure has a poor prognosis, and effective treatments have not been established. Because DOX shows cumulative cardiotoxicity, we hypothesized that minimal cardiac remodelling occurred at the initial stage in activating cardiac fibroblasts. Our aim was to investigate the initial pathophysiology of DOX-exposed cardiac fibroblasts and propose prophylaxis.

Methods and results

An animal study was performed using a lower dose of DOX (4 mg/kg/week for 3 weeks, i.p.) than a toxic cumulative dose. Histological analysis was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay, picrosirius red staining, and immunohistochemical staining. The mechanism was analysed in vitro with a low dose of DOX, which did not

SUBMITTER: Tanaka R 

PROVIDER: S-EPMC7160475 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature