Characterizing Cardiolipin Species in the Hearts After Anthracycline Administration

Abstract Objectives Anthracyclines damage the heart by binding to the inner mitochondrial membrane phospholipid cardiolipin and promoting mitochondrial dysfunction. Our goal is to characterize how anthracylcines change the fatty acid profile of cardiolipin, and the genes controlling cardiolipin synthesis and remodeling in order to develop dietary strategies to target cardiolipin within damaged hearts. Methods Male C57BL/6J mice were randomized to receive seven IP, anthracycline injections (one week apart) or saline control injections. Six hours after the final injection, mice were euthanized under isoflurane and hearts were collected for mRNA and cardiolipin species analysis. Cardiolipin was measured using liquid chromatography coupled to electrospray ionization mass spectrometry in an API 4000 mass spectrometer (Sciex, Framingham, MA). A student's t-test was used to determine significance between the groups. Results While the amount of tetralinolylcardiolipin (the major cardiolipin species in the heart) was not altered with anthracycline treatment, several other cardiolipin species were significantly increased, including cardiolipin species that contain arachidonic acid and docosahexaenoic acid. In addition we observed a significant decrease in the proportion of monolysocardiolipin species in the heart and a trend towards increased oxidized cardiolipin species given anthracycline treatment. Conclusions Previous studies have shown the fatty acid composition of cardiolipin effects mitochondrial structure and function. Administration of anthracyclines alters cardiolipin species in the heart. Knowing that anthracyclines influences the fatty acid composition of cardiolipin, we can explore dietary interventions that favorably change cardiolipin fatty acid composition, with the goal of preventing anthracycline-induced heart damage by improving mitochondrial function. Funding Sources Funding was provided by NIH R21CA185140, Ohio Agriculture Research and Development Center, the Carol S. Kennedy Professorship, and the Ohio State University Education and Human Ecology Dissertation Research Fellowship.