Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA

Exp Mol Med. 2002 Sep 30;34(4):278-84. doi: 10.1038/emm.2002.39.

Abstract

Direct injection of the vascular endothelial growth factor (VEGF) gene plasmid DNA into the myocardium was shown to induce development of new blood vessels to increase the circulation in the heart of patients with coronary artery diseases. However, such angiogenic gene therapy (via naked DNA) was limited by low level of gene expression. Furthermore, the temporal and spatial characteristics of VEGF gene transfer in the heart are not known. In this study, we demonstrated that a plasmid vector, containing the human cytomegalovirus immediate early (HCMV IE) promoter and enhancer, induces greater expression of gene in the rat heart monitored by gene fused to the chloramphenicol acetyl transferase (CAT) reporter, than four different viral and cellular promoters. Interestingly, expression of VEGF121 protein showed an earlier peak, a shorter duration, and a wider distribution than that of CAT only. Therefore, a plasmid vector with an HCMV IE promoter/enhancer provides clear advantages over other previously developed plasmids. Furthermore, expression profile of VEGF121 gene may provide useful information in the design of angiogenic gene therapy in the heart.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Artificial Gene Fusion
  • Chloramphenicol O-Acetyltransferase / analysis
  • Chloramphenicol O-Acetyltransferase / genetics
  • Cytomegalovirus / genetics*
  • DNA, Viral / administration & dosage*
  • DNA, Viral / genetics*
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / genetics*
  • Enhancer Elements, Genetic*
  • Gene Expression Regulation, Viral
  • Gene Transfer Techniques*
  • Genes, Viral
  • Genetic Vectors
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Lymphokines / analysis
  • Lymphokines / genetics*
  • Male
  • Myocardium / metabolism*
  • Plasmids / genetics
  • Promoter Regions, Genetic*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • DNA, Viral
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Chloramphenicol O-Acetyltransferase