2009/07/23

PHDs silencing promotes therapeutic revascularisation

Therapeutic neovascularisation represents an alternative treatment modality for patients with advanced ischemic coronary or peripheral artery occlusive disease. The hypoxia-inducible transcription factor (HIF) is a master regulator controlling genes involved in several processes that promote neovascularisation, making modulation of HIF activity an attractive approach for the treatment of ischemic diseases.

The O2-dependent hydroxylase domain proteins (PHDs) control HIF expression. These enzymes hydroxylate and trigger HIF proteasome-dependent degradation.

Researchers from CIC bioGUNE's Cell Biology and Stem Cells unit in collaboration with the INSERM U970 and CNRS UMR6543, France, investigated whether inhibition of PHDs via upregulating HIF might promote postischemic revascularization. Mice with right femoral artery ligation were treated with specific inhibitors of PHDs (siPHDs).

The work showing that silencing of PHDs by the transient and local upregulation of endogenous HIF1α improves vessel growth in ischemic tissues has been published in Circulation (2009; 120:50-59).