: Percutaneous coronary intervention (PCI) is now the dominant revascularisation therapy for coronary artery disease, with nearly 3 million PCIs undertaken per annum world-wide. One of the last remaining challenges to PCI success is in cases of chronic total occlusions (CTO), where average UK success rates are around 66% (BCIS Data). It is only in the more experienced hands that success rates of 80-90% are achieved (EuroCTO club data).There is a need to develop alternative, effective therapies for CTO failures and to this end we have explored therapeutic angiogenesis to enhance antegrade collateral circulation and provide symptom relief in difficult CTO cases. We have investigated the stimulation of endothelial cell (EC) angiogenesis via stabilisation of hypoxia inducible factor (HIF) using two prolyl-hydroxylase inhibitors (PHI). We previously reported that di-methyl oxalylglycine (DMOG) loaded onto a polymer-coated stent increased collateral neovascularisation in a porcine CTO model. We now describe the actions of the PHI FG-2216/BIQ, which unlike DMOG has already been approved for use in man being trialled in patients with renal anaemia. Human umbilical vein endothelial cells (HUVECs) were cultured on growth factor reduced Matrigel in the presence of FG-2216 at a range of doses (from 0 to 500 μM). Endothelial cell (EC) tubule formation was measured at 6 h by image analysis of photomicrographs (image J). Western blotting was used to assess expression of HIF-1α in HUVEC after treatment with 500 μM FG-2216/BIQ for up to 24 h. Quantitative real time RT-PCR (qPCR) was used to examine the expression of vascular endothelial cell growth factor (VEGF) mRNA from treated HUVEC (up to 24 h). We report that as with DMOG, FG-2216 has a dose response, pro-angiogenic effect on HUVEC, with significantly enhanced tubule formation on Matrigel, compared to control (107 vs 21, p
