Tanaka R, Umemura M, Narikawa M, et al. - Given a poor prognosis of doxorubicin (DOX)-induced heart failure has been reported, and there is a lack of established effective treatments, and since DOX displays cumulative cardiotoxicity, researchers formulated a hypothesis that minimal cardiac remodelling happened at the initial stage in activating cardiac fibroblasts, and they undertook this inquiry to determine the initial pathophysiology of DOX-exposed cardiac fibroblasts and propose prophylaxis. Utilizing a lower dose of DOX (4 mg/kg/week for 3 weeks, i.p.) vs a toxic cumulative dose, they conducted an animal study. They found that cell death was not induced by low-dose DOX, and fibrosis was confined to the perivascular area in mice. As per the findings in microarray analysis, a link of DOX induced genes with the innate immune system and inflammatory reactions was suggested, causing cardiac remodelling. Mitochondrial damage and a rise in the expression of interleukin-1 were brought about by DOX. The expression of fibrotic markers, such as alpha smooth muscle actin and galectin-3, was promoted by DOX. The induction of these responses happened via stress-activated protein kinase/c-Jun NH2-terminal kinase signalling. Overall, findings revealed reactive fibrosis was induced by low-dose DOX via sterile inflammation provoked by the damaged mitochondria.