Cardiovascular diseases are the major
cause of death in the western world and produce furthermore the
highest medical costs among all diseases. About 41% of all deaths
in Germany in the year 2010 can be attributed to cardiovascular
diseases. About 17% of these deaths were caused by myocardial
infarction. Cardiac tissue protection in case of acute ischemia
could therefore result in better short and long term survival of
these patients.
In 2003 it was described for the first time that the
Hypoxia-inducible factor (HIF), a heterodimeric transcription
factor, which is stabilized under hypoxic conditions, e.g. in
myocardial infarction, can mediate cardioprotection. It was shown
that the cardioprotective effect of intermittent hypoxia is
dependent on the HIF-1α gene dosage. This was shown by a better
ventricular contractile function and a significantly smaller
infarct size following ischemia-reperfusion in mice pretreated with
intermittent hypoxia. Since then a lot of subsequent papers have
been published that demonstrate the crucial role for HIF-1 in
various modalities of cardioprotection. With the discovery of the
HIF regulating proly-4 hydroxylase domain (PHD) enzymes 1-3
potential therapeutic targets to modulate HIF-1α stability and thus
possibilities to improve ischemic diseases have been discovered.
Despite these findings a lot of open questions remain that will be
addressed in my PhD thesis.
