NDLI: Hypoxia-Inducible Vascular Endothelial Growth Factor Gene Therapy Using the Oxygen-Dependent Degradation Domain in Myocardial Ischemia

Content Provider	Springer Nature Link
Author	Kim, Hyun Ah Lim, Soyeon Moon, Hyung Ho Kim, Sung Wan Hwang, Ki Chul Lee, Minhyung Kim, Sun Hwa Choi, Donghoon
Copyright Year	2010
Abstract	A hypoxia-inducible VEGF expression system with the oxygen-dependent degradation (ODD) domain was constructed and tested to be used in gene therapy for ischemic myocardial disease.Luciferase and VEGF expression vector systems were constructed with or without the ODD domain: pEpo-SV-Luc (or pEpo-SV-VEGF) and pEpo-SV-Luc-ODD (or pEpo-SV-VEGF-ODD). In vitro gene expression efficiency of each vector type was evaluated in HEK 293 cells under both hypoxic and normoxic conditions. The amount of VEGF protein was estimated by ELISA. The VEGF expression vectors with or without the ODD domain were injected into ischemic rat myocardium. Fibrosis, neovascularization, and cardiomyocyte apoptosis were assessed using Masson’s trichrome staining, α-smooth muscle actin (α-SMA) immunostaining, and the TUNEL assay, respectively.The plasmid vectors containing ODD significantly improved the expression level of VEGF protein in hypoxic conditions. The enhancement of VEGF protein production was attributed to increased protein stability due to oxygen deficiency. In a rat model of myocardial ischemia, the pEpo-SV-VEGF-ODD group exhibited less myocardial fibrosis, higher microvessel density, and less cardiomyocyte apoptosis compared to the control groups (saline and pEpo-SV-VEGF treatments).An ODD-mediated VEGF expression system that facilitates VEGF-production under hypoxia may be useful in the treatment of ischemic heart disease.
Starting Page	2075
Ending Page	2084
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	27
Issue Number	10
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2010-07-07
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biomedical Engineering Medical Law Biochemistry Pharmacy Pharmacology/Toxicology
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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