Conditional HIF-1α Expression Produces a Reversible Cardiomyopathy

摘要: 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 mutated, oxygen-stable, form HIF-1a. Cardiac function steadily decreased transgene expression, but recovered after was turned off. Using long-oligo microarrays, we identified 162 transcripts more than 3-fold dysregulated these hearts expression. Among down-regulated genes transcript for SERCA reduced 46% and protein 92%. This led us an evaluation calcium flux that showed diminished reuptake cytoplasmic myocytes from hearts, suggesting mechanism cardiac dysfunction. Conclusions/Significance: These results provide deeper understanding transcriptional activity HIF heart, show enhanced HIF-1 sufficient cause contractile dysfunction adult heart. stabilized myocardium patients ischemic cardiomyopathy, our suggest could be contributing directly this disease.