Tissue hypoxia occurs where there is an imbalance between oxygen supply and consumption in both, solid tumors as a result of exponential cellular proliferation and in atherosclerotic diseases as a result of inefficient blood supply. Hypoxia-inducible factor 1 (HIF-1) is central in normal angiogenesis and cancer angiogenesis. HIF-1 is a transcriptional activator composed of an O 2 -and growth factor-regulated HIF-1a subunit and a constitutively expressed HIF-1b subunit. Upon activation, HIF-1 drives the expression of genes controlling cell survival and governing the formation of new blood vessels. A better understanding of the regulation of HIF-1a levels by the receptor tyrosine kinases/phosphatidylinositol 3-kinase signaling pathway and by the HIF prolyl hydoxylases has provided new insights into the development of anticancer and revascularization therapeutics. We will focus on the potential of a new pharmacology for regulating HIF pathways in both, cancer and ischemic cardiac diseases. The consequences of the switch of HIF activation in these two disease states and the signaling pathway overlap that atherosclerosis and cancer angiogenesis share are discussed.

The objective of this study was to assess event-free survival and total treatment costs of retroinfusion-supported stenting in high-risk patients compared to bypass surgery. An increasing number of patients with main-stem and main-stem-equivalent stenosis are treated by stent implantation, which appears to be safe in the short-term follow-up. However, there is a lack of randomized studies comparing conventional bypass surgery with stent implantation, particularly in patients with high risk for both treatments. We here report on the 1-year results of a prospective randomized single-center study in patients with symptomatic main-stem and main-stem-equivalent lesions with substantially increased risk for bypass surgery. Patients where randomized to undergo either percutaneous transluminal coronary angioplasty/stent procedure (n = 23) or bypass surgery (n = 21). Patients randomized to stent implantation were supported by selective pressure-regulated retroinfusion of the anterior cardiac vein during ischemia. Patients of the stent group and the bypass group did not differ in baseline characteristics, including Parsonnet score and quality-of-life score. Twenty-eight-day mortality and 1-year mortality rate as well as quality-of-life scores were similar in both groups. Event-free survival after 1 year was higher in the bypass group (71.4% vs. 52.3%; P = 0.02) due to a lower target lesion revascularization rate. With regard to total treatment costs, however, the stent group compared favorably to the bypass group (9,346 +/- 807 vs. 26,874 +/- 3,985 euro), predominantly as a result of a shorter intensive care and hospital stay. In this first randomized study in high-risk patients for stent implantation and bypass surgery, patients with retroinfusion-supported stent implantation had a similar 1-year outcome and quality of life compared to patients with bypass surgery. Though in the stent group event-free survival was lower and target lesion revascularization rate was higher, retroinfusion-supported stent implantation was associated with substantially lower costs and might be considered as an alternative treatment option in this selected group of high-risk patients.