Background: 

The hypoxia-inducible factor (HIF)-1 is critically involved in the cellular adaptation towards a decrease in oxygen availability. The influence of HIF for the development of cardiac hypertrophy and cardiac function in response to sustained hemodynamic overload is largely unknown.

Methods and Results: 

HIf-1a+/+ and HIf-1a+/­ mice were studied regarding cardiac hypertrophy, cardiac function and expression of Ca²⁺-handling proteins after subjected to transverse aortic constriction (TAC). After TAC HIf-1a+/+ and HIf-1a+/­ mice developed cardiac hypertrophy with increased posterior wall thickness and septum thickness. No significant difference in cardiac vessel density was observed between HIf-1a+/+ and HIf-1a+/­ mice. However, just the HIf-1a+/­ mice developed severe heart failure as revealed by a significantly reduced fractional shortening, which was mostly due to increased end-systolic left ventricular dimensions. This correlated to a modulated SERCA2a protein expression in the HIf-1a+/­ mice.

Conclusions: 

HIF-1a is critically involved in the preservation of cardiac function during chronic pressure overload. This effect seems to be mediated at least partly via HIF-dependent modulation of Ca²⁺-handling.