Role of hypoxia-inducible factor in diabetic myocardial hypertrophy

Abstract

Purpose: This study was carried out to investigate the role of hypoxia-inducible factor (HIF) in diabetic cardiomyopathy in vitro.

Methods: Hypoxia was induced chemically in H9C2 cells (cardiac hypertrophy model), and the cells were treated with phenylephrine (PE), deferoxamine (DFO), PE + DFO, and HIF-1α siRNA under conditions of high and normal glucose. Western blot was used to analyze the expression of some glycolytic proteins, including Glut-1, hexokinase (HXK-2), and enolase, while apoptosis of H9C2 was determined by flow cytometry.

Results: PE caused hypertrophy in H9C2, which was ameliorated by HIF-1α. Compared to normal, under prolonged high glucose, the low expression of HIF-1α led to low expressions of Glut-1, HXK-2 and enolase. However, expression of HIF-1α decreased, while those of Bax and Caspase 3 increased, and Bcl-2 expression decreased. Furthermore, under short time high glucose, HIF-1α caused apoptosis of hypertrophic cardiomyocytes.

Conclusion: HIF-1 mediates diabetic myocardial hypertrophy, probably as a function of the degree of high glucose exposure and hypoxia.

Keywords: H9C2 cardiomyocyte, Hypoxia-inducible factor, Myocardial hypertrophy, Diabetic cardiomyopathy