Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration.
Adeno-associated virus serotype 8 ApoA-I gene transfer reduces progression of atherosclerosis in ApoE-KO mice: comparison of intramuscular and intravenous administration.
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腺相关病毒血清型 8 ApoA-I 基因转移可减少 ApoE-KO 小鼠动脉粥样硬化的进展：肌肉注射和静脉注射的比较。
DOI：
10.1097/fjc.0b013e3182092841
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发表时间：
2011
影响因子：
3
通讯作者：
Badimon,JuanJ
中科院分区：
文献类型：
--
作者：
Cimmino,Giovanni;Giannarelli,Chiara;Chen,Wei;Alique,Matilde;Santos-Gallego,CarlosG;Fuster,Valentin;Hajjar,RogerJ;Walsh,ChristopherE;Badimon,JuanJ
载脂蛋白AI（ApoA-I）/高密度脂蛋白（HDL）升高治疗是有效的抗动脉粥样硬化策略。我们比较了门静脉内和肌肉内基因转移的人ApoA-I（hApoA-I）过表达在动脉粥样硬化ApoE基因敲除小鼠中的抗动脉粥样硬化作用。动脉粥样硬化病变由致动脉粥样硬化饮食诱导。动脉粥样硬化诱导后，处死一组动物作为动脉粥样硬化基线对照组。其余动物随机分为以下组：（1）动脉粥样硬化-进展-对照组，（2）门静脉内/载体给药组，和（3）肌内/载体给药组。主动脉和心脏分别用表面苏丹IV和油红-O进行动脉粥样硬化定量处理。处理肝脏和肌肉标本进行蛋白质/基因表达分析。在两个转导组中观察到hApoA-I/HDL血浆水平的持续增加。与进展对照组相比，hApoA-I过表达消除了斑块进展。hApoA-I过表达显著减少了病变巨噬细胞，其特征指示斑块稳定。与进展对照组相比，处理组中B类I型清道夫受体（SR-BI）而非ATP结合盒亚家族A（ABCA）成员1（ABCA-1）显著上调。本研究的结果显示，通过2种不同的给药途径，hApoA-I/HDL过表达对斑块进展/稳定的影响相似。我们的研究结果显示，使用肌肉注射和门静脉内给药途径的相似效果可能具有显著的临床意义，因为肌肉注射降低了患者的医疗风险和成本。
Apolipoprotein AI (ApoA-I)/high-density lipoprotein (HDL)-raising treatments are effective antiatherosclerotic strategies. We have compared the antiatherogenic effects of human ApoA-I (hApoA-I) overexpression by intraportal and intramuscular gene transfer in atherosclerotic ApoE-knockout mice. Atherosclerotic lesions were induced by atherogenic diet. After atherosclerosis induction, a group of animals was killed and served as atherosclerosis baseline-control group. The remaining animals were randomized into the following groups:(1) atherosclerosis-progression-control,(2) intraportal/vector administration, and (3) intramuscular/vector administration. Aortas and hearts were processed for atherosclerotic quantification by en face Sudan IV and Oil Red-O, respectively. Liver and muscle specimens were processed for protein/gene expression analysis. A sustained increase in hApoA-I/HDL plasma levels was observed in both transduced groups. hApoA-I overexpression abolished plaque progression versus progression-control group. hApoA-I overexpression significantly reduced lesion macrophage, feature indicative of plaque stabilization. Scavenger receptor class-B type I (SR-BI), but not ATP-binding cassette, sub-family A (ABCA), member 1 (ABCA-1), was significantly upregulated in treated groups versus progression-controls. The results of this study show a similar effect of hApoA-I/HDL overexpression on plaque progression/stabilization by 2 different routes of administration. Our results showing similar effects using either intramuscular administration and intraportal route of administration may have significant clinical implications, given the reduced medical risk to patient and cost of intramuscular injections.