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Heart failure represents a major health problem. The development of new drugs to treat this condition is essential. We previously discovered that AF-001 attenuates the cardiac defects caused by heart failure in zebrafish. In this paper, we report the identification of AF-HF001, an AF-001 derivative, and its effects on live cardiomyocytes subjected to oxidative damage. The in vitro results demonstrated that AF-HF001 attenuates the production of reactive oxygen species (ROS) and the myocardial cell apoptosis. A DNA microarray was performed to broadly analyze gene expression after H2O2 treatment with or without AF-HF001. Hierarchical clustering analysis revealed that AF-HF001 modifies the expression of certain genes (Ndufs2, Ndufb6, Ndufb8, Ndufa13, Ndufs3, Ndufs5, TPM1, MYH14, RyR1, and TIMP4) related to ROS production, cardiac contractility and extracellular matrix remodeling. AF-HF001 ameliorates oxidative damage, which may be related to the mitogen-activated protein kinase (MAPK) family and the intrinsic mitochondrial pathway. Altogether, this study suggests that AF-HF001 exhibits potential as a clinical drug candidate for the treatment of heart failure. |
