Reduction in the extent of atherosclerosis in apolipoprotein E-deficient mice induced by electroporation-mediated transfer of the human plasma platelet-activating factor acetylhydrolase gene into skeletal muscle.
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.
Hase
Makoto
M
Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan.
Tanaka
Masashi
M
Yokota
Mitsuhiro
M
Yamada
Yoshiji
Y
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control; D004036:Diet, Atherogenic; D018274:Electroporation; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000097:blood / Q000235:genetics*; D020298:U937 Cells
D001057:Apolipoproteins E; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase