Polymeric gene delivery of ischemia-inducible VEGF significantly attenuates infarct size and apoptosis following myocardial infarct
| Autor: | Harold M. Erickson, Minhyung Lee, Aida Albanil, James W. Yockman, Donghoon Choi, Andrew Kastenmeier, Matthew G. Whitten, Chien-Wen Chang, David A. Bull, Sung Wan Kim |
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| Rok vydání: | 2008 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Polymers Genetic enhancement Myocardial Infarction Ischemia Gene Expression Infarction Apoptosis Gene delivery Transfection Cell Line Injections chemistry.chemical_compound Internal medicine Genetics medicine Animals cardiovascular diseases Myocardial infarction Molecular Biology business.industry Myocardium Genetic Therapy medicine.disease Vascular endothelial growth factor medicine.anatomical_structure chemistry Ventricle Models Animal Cardiology Molecular Medicine Rabbits Ligation business |
| Zdroj: | Gene Therapy. 16:127-135 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/gt.2008.146 |
| Popis: | 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 (P0.001). The use of a non-viral carrier to deliver an ischemia-inducible VEGF construct is effective in the treatment of acutely ischemic myocardium. |
| Databáze: | OpenAIRE |
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