Early Biomarkers of Doxorubicin-Induced Heart Injury

NCTR scientists, in collaboration with the National Cancer Institute, Korea University, and the Arkansas Heart Hospital, utilized a mouse model of doxorubicin (DOX)-induced heart injury to develop candidates for early biomarkers of DOX cardiotoxicity. The most effective use of this chemotherapeutic is now strictly limited by general estimates of toxicity to patients. The investigators demonstrated a dose-dependent increase in the expression of a pro-apoptotic (likely leading to cell death) microRNA (miR-34a) in the heart prior to an increase in troponin T plasma levels and development of cardiac pathology. Additionally, a panel of 12 miRNAs implicated with hypertrophy (enlargement of an organ or tissue), were differentially expressed prior to pathological evidence of cardiac hypertrophy.

This study suggests a combination of apoptosis, hypertrophy, fibrosis (thickening and scarring of tissue), and vacuolization (formation of small cavity in a cell containing air or fluid) may contribute to the development of cardiac impairment due to DOX-treatment. Early biomarkers of DOX-induced heart injury with potential applications in the clinic for monitoring and/or predicting cardiotoxicity induced by DOX will produce more effective treatment regimens. A paper describing this study is available online at Toxicology and Applied Pharmacology.

For additional information, please contact Varsha Desai, Ph.D., Personalized Medicine Branch, Division of Systems Biology, FDA/NCTR.