Journal
PROSTAGLANDINS & OTHER LIPID MEDIATORS
Volume 70, Issue 1-2, Pages 107-118Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0090-6980(02)00015-1
Keywords
platelet-activating factor acetylhydrolase; apolipoprotein E-deficient; atherosclerosis
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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 mug 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. (C) 2002 Elsevier Science Inc. All lights reserved.
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