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Background Cardiac hypertrophy is an important pre-pathology of heart failure, which will ultimately lead to heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. The aim of this study is to elucidate the effects and mechanisms of histidine triad nucleotide binding protein 1 (HINT1) in cardiac hypertrophy and heart failure. Methods HINT1 was down-regulated in human hypertrophic heart samples compared with non-hypertrophic samples by mass spectrometry analysis. Hint1 knockout mice were c