Why the study?
Doxorubicin use is limited by dose-dependent cardiotoxicity, but its effects and mechanisms on cardiac extracellular matrix homeostasis and remodeling remain poorly understood compared with its toxicity in cardiomyocytes.
Does doxorubicin alter extracellular matrix regulation and collagen production in primary cardiac fibroblasts from mice?
Does doxorubicin alter extracellular matrix regulation and collagen production in primary cardiac fibroblasts from mice?
Doxorubicin induces significant changes in the cardiac fibroblast proteome and increases collagen production, providing mechanistic insights into DOX-induced cardiotoxicity and ECM remodeling.
DOX alters ECM gene expression and collagen production in fibroblasts in vitro; leaves open contribution to clinical cardiotoxicity.
OBJECTIVE: Doxorubicin (DOX) is a highly effective chemotherapeutic used to treat many adult and pediatric cancers. However, its use is limited due to a dose-dependent cardiotoxicity, which can lead to lethal cardiomyopathy. In contrast to the extensive research efforts on toxic effects of DOX in cardiomyocytes, its effects and mechanisms on cardiac extracellular matrix (ECM) homeostasis and remodeling are poorly understood. In this study, we examined the potential effects of DOX on cardiac ECM to further our mechanistic understanding of DOX-induced cardiotoxicity. RESULTS: . Quantitative proteomics analysis revealed significant global changes in the fibroblast proteome following DOX treatment. A pathway analysis using iPathwayGuide of the differentially expressed proteins revealed changes in a list of biological pathways that involve cell adhesion, cytotoxicity, and inflammation. An apparent increase in Picrosirius red staining indicated that DOX-induced an increase in collagen production in cardiac primary fibroblasts after 3-day treatment. No significant changes in collagen organization nor glycoprotein production were observed.
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Skaggs et al. (2023) studied this question.
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