Exp Mol Med.
2002 Sep;34(4):278-284.
Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA
- Affiliations
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- 1Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea. dkkim@smc.samsung.co.kr
- 2Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Laboratory of Cardiovascular Molecular Therapy, MTRC and SBRI, Seoul, Korea.
- 3Department of Bioscience, Sejong University, Seoul, Korea.
- 4Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
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
Keyword
MeSH Terms
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Animals
Chloramphenicol O-Acetyltransferase/analysis/genetics
Comparative Study
Cytomegalovirus/*genetics
DNA, Viral/*administration & dosage/*genetics
Endothelial Growth Factors/analysis/*genetics
*Enhancer Elements (Genetics)
Gene Expression Regulation, Viral
Gene Fusion
*Gene Transfer Techniques
Genes, Viral
Genetic Vectors
Intercellular Signaling Peptides and Proteins/analysis/*genetics
Lymphokines/analysis/*genetics
Male
Myocardium/*metabolism
Plasmids/genetics
*Promoter Regions (Genetics)
Rats
Rats, Sprague-Dawley
Time Factors
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
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