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Through this study, we showed the synergistic role of HIF\u20101\u03b1 and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi\u2010quantitative reverse transcriptase polymerase chain reaction (RT\u2010PCR), Western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF\u20101\u03b1 and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death. 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