Cardiomyocyte death is an important pathogenic feature of ischemia and heart failure. Through this study, we showed the synergistic role of HIF-1α and FoxO3a in cardiomyocyte apoptosis subjected to hypoxia plus elevated glucose levels. Using gene specific small interfering RNAs (siRNA), semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blot, immunofluorescence, nuclear and cytosolic localization and TUNEL assay techniques, we determined that combined function of HIF-1α and FoxO3a under high glucose plus hypoxia condition lead to enhanced expression of BNIP3 inducing cardiomyocyte death. Our results highlighted the importance of the synergistic role of HIF-1α and FoxO3a in cardiomyocyte death which may add insight into therapeutic approaches to pathophysiology associated with ischemic diabetic cardiomyopathies.
Keywords: BCL2/Adenovirus E1B Nineteen kilo Dalton Interacting Protein 3 (BNIP3); diabetic hyperglycemic; forkhead box O3 (FoxO3); hyperglycemia; hypoxia-inducible factor-1 alpha (HIF-1α); ischemia hypoxia.
© 2017 Wiley Periodicals, Inc.