Cardiac functions of the cellular oxygen sensors prolyl-4-hydroxylase domain enzymes 2 and 3

Kardiale Funktionen der zellulären Sauerstoffsensoren Proly-4-Hydroxylase-Domäne Enzyme 2 und 3

by Marion Hölscher
Doctoral thesis
Date of Examination:2012-06-06
Date of issue:2012-07-24
Advisor:Prof. Dr. Dörthe Katschinski
Referee:Prof. Dr. Stefanie Pöggeler
Referee:Prof. Dr. Frauke Alves
Referee:Prof. Dr. Dörthe Katschinski
Persistent Address: http://dx.doi.org/10.53846/goediss-1434

 

 

Files in this item

Name:hoelscher.pdf
Size:10.1Mb
Format:PDF

The following license files are associated with this item:

Abstract

English

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.
Keywords: PHD2; PHD3; HIF
Schlagwörter: PHD2; PHD3; HIF
 
Statistik