Abstract:
:The hypoxia-inducible transcription factor HIF is induced early in acute myocardial ischemia in humans, but it is unknown whether this activation of HIF persists during chronic heart failure. The HIF system was characterized in left ventricular myocardia from 18 explanted failing hearts and 11 non-failing donor hearts by quantitative RT-PCR and Western analysis. HIF-1alpha mRNA levels were significantly decreased while its natural antisense transcript aHIF was nearly twofold higher (p<0.01) in failing myocardia than in control hearts. Moreover, compared to donor hearts a significantly increased expression of HIF-3alpha, which may act as a competitive inhibitor of HIF-1/2alpha activity, and PHD3, which upon hydroxylation of prolyl residues directs HIF-alpha subunits towards proteasomal degradation, was observed in the failing myocardium. Although negative regulators of HIF were induced, the HIF pathway obviously remains activated in chronic human heart failure, because prototype HIF target genes, such as ABCG2, VEGF, and BNIP3, were significantly induced.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Zolk O,Solbach TF,Eschenhagen T,Weidemann A,Fromm MFdoi
10.1016/j.bbrc.2008.08.152subject
Has Abstractpub_date
2008-11-14 00:00:00pages
315-20issue
2eissn
0006-291Xissn
1090-2104pii
S0006-291X(08)01689-6journal_volume
376pub_type
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