Conditional HIF-1alpha expression produces a reversible cardiomyopathy.

ABSTRACT:

Background

The response to hypoxia in tissues is regulated by the heterodimeric transcription factor Hypoxia Inducible Factor-1 (HIF-1).

Methodology/principal findings

We have created a strain of mice with inducible cardiomyocyte-specific expression of a mutated, oxygen-stable, form of HIF-1alpha. Cardiac function steadily decreased with transgene expression, but recovered after the transgene was turned off. Using long-oligo microarrays, we identified 162 transcripts more than 3-fold dysregulated in these hearts after transgene expression. Among the down-regulated genes the transcript for SERCA was reduced 46% and the protein 92%. This led us to an evaluation of calcium flux that showed diminished reuptake of cytoplasmic calcium in myocytes from these hearts, suggesting a me

SUBMITTER: Bekeredjian R 

PROVIDER: S-EPMC2908132 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature