Abstract |
The development of clinically beneficial myocardial gene therapy has been slowed by reliance on the use of viral carriers and non-physiologic, constitutive gene expression. To specifically address these issues, we have developed a non-viral gene carrier, water-soluble lipopolymer (WSLP), and an ischemia-inducible plasmid construct expressing vascular endothelial growth factor ( VEGF), pRTP801-VEGF, to treat myocardial ischemia and infarction. Rabbits underwent ligation of the circumflex artery followed by injection of (a) an ischemia-inducible VEGF gene construct in a WSLP carrier; (b) a constitutively expressed, or unregulated, SV- VEGF gene construct in a WSLP carrier; (c) WSLP carrier alone; or (d) no injection therapy. Following 4 weeks treatment, ligation alone resulted in infarction of 48+/-7% of the left ventricle. With injection of WSLP carrier alone, 49+/-6% of the left ventricle was infarcted (P=NS). The constitutively expressed gene construct, SV- VEGF, reduced the infarct size to 32+/-7% of the left ventricle (P=0.007). The ischemia-inducible gene construct, RTP801-VEGF, further reduced the infarct size to 13+/-4% of the left ventricle (P<0.001). The use of a non-viral carrier to deliver an ischemia-inducible VEGF construct is effective in the treatment of acutely ischemic myocardium.
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Authors | J W Yockman, D Choi, M G Whitten, C W Chang, A Kastenmeier, H Erickson, A Albanil, M Lee, S W Kim, D A Bull |
Journal | Gene therapy
(Gene Ther)
Vol. 16
Issue 1
Pg. 127-35
(Jan 2009)
ISSN: 1476-5462 [Electronic] England |
PMID | 18784748
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Polymers
- Vascular Endothelial Growth Factor A
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Topics |
- Animals
- Apoptosis
- Cell Line
- Gene Expression
- Genetic Therapy
(methods)
- Injections
- Models, Animal
- Myocardial Infarction
(metabolism, pathology, therapy)
- Myocardium
(metabolism, pathology)
- Polymers
- Rabbits
- Transfection
(methods)
- Vascular Endothelial Growth Factor A
(analysis, genetics)
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