Hase Makoto, Tanaka Masashi, Yokota Mitsuhiro, Yamada Yoshiji
Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan.
Prostaglandins Other Lipid Mediat. 2002 Sep;70(1-2):107-18. doi: 10.1016/s0090-6980(02)00015-1.
The effect of increasing the activity of plasma platelet-activating factor (PAF) acetylhydrolase (AH) (PAF-AH) on the progression of atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice was examined by gene delivery to skeletal muscle. The expression vector pcDNA3.1 containing either human PAF-AH cDNA (pcDNA/PAF-AH) or green fluorescent protein cDNA (pcDNA/GFP) was introduced into the skeletal muscle of both hind legs of 6-week-old apoE(-/-) mice by electroporation. The activity of PAH-AH in plasma was significantly increased 4-16 weeks after electroporation of apoE(-/-) mice with 120 microg of pcDNA/PAF-AH; the maximal (2.5-fold) increase was apparent after 8 weeks. The mean thickness of the aortic wall, determined by 160 measurements in each mouse, was significantly reduced in apoE(-/-) mice 8-16 weeks after exposure to pcDNA/PAF-AH compared with that in corresponding control animals that received pcDNA/GFP. These results suggest that the electrotransfer of the plasma PAF-AH gene to skeletal muscle reduces the extent of atherosclerosis in apoE(-/-) mice.
通过将基因导入骨骼肌，研究了提高血浆血小板活化因子（PAF）乙酰水解酶（AH）（PAF-AH）活性对载脂蛋白E缺陷（apoE(-/-)）小鼠动脉粥样硬化进展的影响。通过电穿孔将含有人类PAF-AH cDNA（pcDNA/PAF-AH）或绿色荧光蛋白cDNA（pcDNA/GFP）的表达载体pcDNA3.1导入6周龄apoE(-/-)小鼠两条后腿的骨骼肌中。用120微克pcDNA/PAF-AH对apoE(-/-)小鼠进行电穿孔后4至16周，血浆中PAH-AH的活性显著增加；8周后出现最大（2.5倍）增加。与接受pcDNA/GFP的相应对照动物相比，在接触pcDNA/PAF-AH后8至16周，通过对每只小鼠进行160次测量确定的主动脉壁平均厚度在apoE(-/-)小鼠中显著降低。这些结果表明，将血浆PAF-AH基因电转移至骨骼肌可减轻apoE(-/-)小鼠的动脉粥样硬化程度。
