Viral vector-mediated overexpression of mitochondrial ATP-binding cassette subfamily B member7 does not protect against doxorubicin-induced cardiotoxicity

• DOI: 10.1152/physiol.2023.38.s1.5732530
• Publication Date: 2023-05-29T14:52:22Z
• Authors: Imtiaz Masfique D...; Branden Nguyen; Vivian Doerr; Cesar Jacintho Mo...; Ashley Smuder
• Keywords: Cardiotoxicity

Doxorubicin (DOX)-induced cardiotoxicity results in an increased risk of mortality among chemotherapy recipients. Cardiomyocyte dysfunction is caused by the off-target accumulation DOX cardiac mitochondria, stimulating oxidative damage and impaired phosphorylation. Prior research showed that exercise preconditioning may prevent DOX-induced enhancing abundance mitochondrial ATP-binding cassette (ABC) transporters, potentially accelerating rate clearance from cardiomyocytes. Mitochondrial ABC subfamily B member7 (ABCB7) has been implicated drug export multidrug resistance. Therefore, to further understand whether, independent exercise, overexpression a mitochondria-localized transporter can acute cardiotoxic effects DOX, we examined adeno-associated virus (AAV)-mediated ABCB7 on function, tolerance, its metabolites (doxorubicinol) animals treated acutely with (20 mg/kg IP). Female Sprague-Dawley rats were randomized into four experimental groups (n=10/ group): 1) Saline-treatment (CON), 2) DOX-treatment (DOX), 3) overexpression, saline-treatment (ABCB7), 4) (ABCB7+DOX). Our findings show treatment detriments left ventricular fractional shortening percentage 48 hours following administration, could partially protect such dysfunction. However, effect function was not related reduction doxorubicinol concentration, nor does it improve tolerance DOX-treated animals. Further work needed elucidate function. Funding Source: R01 HL144858 This full abstract presented at American Physiology Summit 2023 meeting only available HTML format. There are no additional versions or content for this abstract. involved peer review process.