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

Prostaglandins Other Lipid Mediat. 2002 Sep;70(1-2):107-18. doi: 10.1016/s0090-6980(02)00015-1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Alkyl-2-acetylglycerophosphocholine Esterase
  • Animals
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Arteriosclerosis / etiology
  • Arteriosclerosis / prevention & control
  • Diet, Atherogenic
  • Electroporation
  • Gene Transfer Techniques
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phospholipases A / blood
  • Phospholipases A / genetics*
  • U937 Cells

Substances

  • Apolipoproteins E
  • Phospholipases A
  • 1-Alkyl-2-acetylglycerophosphocholine Esterase