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

A novel adenoviral gutless vector encoding sphingosine kinase promotes arteriogenesis and improves perfusion in a rabbit hindlimb ischemia model
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DOI:
10.1097/00019501-200510000-00006
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发表时间:
2005-11-01
影响因子:
1.8
通讯作者:
Hong, MK
Hong, MK
中科院分区:
医学4区
文献类型:
--
作者:
Lee, JU;Shin, J;Hong, MK

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我们之前在小鼠基质模型中证明了鞘氨醇激酶(SPK)增加细胞外鞘氨醇-1-磷酸水平并促进新生血管的形成。在这项研究中,我们验证了使用一种新型腺病毒“无胆”载体(AGV)转移SPK基因可以促进兔后肢缺血模型的动脉发生的假设。方法35只雄性新西兰大白兔随机分为AGV-SPK组(n=13)、AGV-SPK无效组(n=13)和对照组(n=9)。第10天,诱导单侧后肢缺血后,引入基因载体或缓冲液,第30天通过小牛血压、定量血管造影和组织学检查效果。结果包括agv无效组在内的对照组第30天缺血肢体与正常肢体小腿收缩压之比为0.77 +/- 0.13,AGV-SPK组为0.91 +/- 0.14 (P < 0.05)
Objectives We previously demonstrated that sphingosine kinase (SPK) increases the level of extracellular sphingosine-1-phosphate and promotes neovascularization in a mouse matrigel model. In this study, we tested the hypothesis that SPK gene transfer using a novel adenoviral 'gutless' vector (AGV) can enhance arteriogenesis in a rabbit hindlimb ischemia model.Methods Thirty-five male New Zealand white rabbits were randomized to the AGV-SPK group (n=13), AGV-null group (n=13), and control group (n=9). On day 10, after the induction of unilateral hindlimb ischemia,gene vectors or buffer were introduced and the effect examined on day 30, using calf blood pressure, quantitative angiographic analysis, and histology.Results Calf systolic blood pressure ratios of the ischemic limb to the normal limb on day 30 were 0.77 +/- 0.13 in control groups, including the AGV-null group, and 0.91 +/- 0.14 in the AGV-SPK group (P