Anthracyclines induce global changes in cardiomyocyte chromatin accessibility that overlap with cardiovascular disease loci.

ABSTRACT: Breast cancer drugs including anthracyclines (ACs) and Trastuzumab increase the risk for cardiovascular diseases (CVDs) such as atrial fibrillation (AF) and heart failure (HF) that ultimately affect the heart muscle. These CVDs are associated with hundreds of genetic variants in non-coding regions of the genome. However, how these drugs affect the regulatory potential of the non-coding genome of the heart and CVD risk loci is unknown. We therefore measured global chromatin accessibility across iPSC-derived cardiomyocytes derived from four healthy individuals that we treated with topoisomerase II (TOP2) inhibiting ACs, Doxorubicin, Epirubicin, and Daunorubicin, and the anthracenedione, Mitoxantrone as well as the TOP2-independent monoclonal antibody Trastuzumab, for three and 24 hours. We i

SUBMITTER: Matthews ER 

PROVIDER: S-EPMC12561927 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature