title: Improved expression by cytomegalovirus promoter/enhancer and behavior of vascular endothelial growth factor gene after myocardial injection of naked DNA.
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.
authors.affiliation: Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon 301-721, Korea.
authors.forename: Jin Ok
authors.initials: JO
authors.lastname: Jeong
authors.forename: Jonghoe
authors.initials: J
authors.lastname: Byun
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Gwon
authors.forename: Young Shin
authors.initials: YS
authors.lastname: Lim
authors.forename: Jangwon
authors.initials: J
authors.lastname: Park
authors.forename: Seon-Ju
authors.initials: SJ
authors.lastname: Yeo
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics*; D004279:DNA, Viral / Q000008:administration & dosage* / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques; D005814:Genes, Viral; D005822:Genetic Vectors; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D004279:DNA, Viral; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015500:Chloramphenicol O-Acetyltransferase