Administration of a TLR9 Inhibitor Attenuates the Development and Progression of Heart Failure in Mice

•Under pressure overload, mitochondrial deoxyribonucleic acid containing the unmethylated cytidine-phosphate-guanosine motif is accumulated in cardiomyocytes and stimulates Toll-like receptor 9, resulting in inflammation and heart failure.•Treatment with E6446, (6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole), a specific Toll-like receptor 9 inhibitor, prevented the development and slowed the progression of left ventricular dilatation and cardiac dysfunction in mice after pressure overload.•E6446 attenuated the inflammatory responses in the pressure-overloaded mouse heart, even though the accumulation of mitochondrial deoxyribonucleic acid in cardiomyocytes was observed.•E6446 could be a new therapeutic agent against heart failure.