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

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

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

2010
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Overview
Purpose 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. Methods 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. Results 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). Conclusion An ODD-mediated VEGF expression system that facilitates VEGF-production under hypoxia may be useful in the treatment of ischemic heart disease.
Publisher
Boston : Springer US,Springer US,Springer,Springer Nature B.V
Subject

administration & dosage

/ Animals

/ Apoptosis

/ Biochemistry

/ Biological and medical sciences

/ Biomedical and Life Sciences

/ Biomedical Engineering and Bioengineering

/ Biomedicine

/ biosynthesis

/ Cardiovascular disease

/ Cell Line

/ Disease Models, Animal

/ Enzyme-Linked Immunosorbent Assay

/ Erythropoietin

/ Erythropoietin - genetics

/ Gene expression

/ Gene therapy

/ General pharmacology

/ Genetic Therapy

/ Genetic Therapy - methods

/ Genetic Vectors

/ genetics

/ Humans

/ Hypoxia

/ Hypoxia - metabolism

/ hypoxia-inducible expression

/ Immunohistochemistry

/ In Situ Nick-End Labeling

/ Ischemia

/ ischemic myocardium

/ Luciferases

/ Luciferases - genetics

/ Male

/ Medical Law

/ Medical sciences

/ metabolism

/ methods

/ Myocardial Ischemia

/ Myocardial Ischemia - pathology

/ Myocardial Ischemia - therapy

/ Myocardium

/ Myocardium - metabolism

/ Myocardium - pathology

/ Oxygen

/ Oxygen - metabolism

/ oxygen-dependent degradation domain

/ pathology

/ Pharmaceutical sciences

/ Pharmaceutical technology. Pharmaceutical industry

/ Pharmacology. Drug treatments

/ Pharmacology/Toxicology

/ Pharmacy

/ Plasmids

/ Protein Stability

/ Rats

/ Rats, Sprague-Dawley

/ Research Paper

/ Simian virus 40

/ Simian virus 40 - genetics

/ therapy

/ Transfection

/ Vascular endothelial growth factor

/ Vascular Endothelial Growth Factor A

/ Vascular Endothelial Growth Factor A - administration & dosage

/ Vascular Endothelial Growth Factor A - biosynthesis

/ Vascular Endothelial Growth Factor A - genetics