A major cause of morbidity and mortality in
cardiovascular disease is pathological
cardiac hypertrophy. With an increase in the cellular surface area and upregulation of the
atrial natriuretic peptide (
ANP) gene,
cardiac hypertrophy is a prominent feature of
diabetic cardiomyopathy.
ANP is a hypertrophic marker. Many works have been done to explore how the
glucose induces the
cardiac hypertrophy. However, it is not enough for us to figure it out. In this study, the influences of different
glucose concentrations on cardiomyocytes were examined in vitro. The results showed that cardiomyocytes cultured with 25mM
glucose tended to show a hypertrophic phenotype, while cardiomyocytes cultured with 35mM
glucose tended to undergo apoptosis. An increased expression of SOX9 was observed when cardiomyocytes were cultured with 25mM
glucose, but when the concentration of
glucose was increased to 35mM, the expression of SOX9 decreased. We used the RNAi approach to knockdown SOX9 expression, to assess its effects on cardiomyocyte
hypertrophy. The results showed that knockdown of the SOX9 gene suppressed the 25mM
glucose-induced cardiomyocyte
hypertrophy. The upregulation of the
ANP gene was associated with overexpression of SOX9. Additionally, the results showed that high
glucose (HG, 25mM) treatment increased the expression of
hypoxia-inducible factor (HIF)1a. Further study showed that HIF1a participated in regulating SOX9 expression in response to HG. This study revealed a novel regulatory mechanism of HIF1a-SOX9 in high
glucose-induced cardiomyocyte
hypertrophy, as well as the related molecular mechanisms.