A novel gutless adenoviral vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model

Abstract

Background: We previously demonstrated that sphingosine kinase can increase the level of extracellular sphingosine 1 phosphate and promote arteriogenesis in a mouse model. The present study was designed to test the hypothesis that SPK gene transfer using a novel gutless adenoviral vector can enhance artriogenesis. Methods: 35 male New Zealand White rabbit were assigned to three groups; SPK group(n=13), null group(n=13), and control group(n=9). At day 10 after the induction of unilateral hind-limb ischemia, gene vectors or buffer were introduced and the effect was examined at day 30 suing calf blood pressure, quantitative angiographic analysis and histology. Result: SPK group resulted higher systolic bloos pressure ratio than control groups(0.89+/- 0.04 vs 0.77 +/-0.04, p=0.01) Increased larger neovessels in histology was noted in SPK group(14.7 +/-1.6 vs 12.8+/- 2.5 p=0.54) Conclusion: The result of this study showthat SPK may promote arteriogenesis.