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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-3-26
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pubmed:abstractText |
Although human heme oxygenase-1 (hHO-1) could provide a useful approach for cellular protection in the ischemic heart, constitutive overexpression of hHO-1 may lead to unwanted side effects. To avoid this, we designed a hypoxia-regulated hHO-1 gene therapy system that can be switched on and off. This vigilant plasmid system is composed of myosin light chain-2v promoter and a gene switch that is based on an oxygen-dependent degradation domain from the hypoxia inducible factor-1-alpha. The vector can sense ischemia and switch on the hHO-1 gene system, specifically in the heart. In an in vivo experiment, the vigilant hHO-1 plasmid or saline was injected intramyocardially into myocardial infarction mice or sham operation mice. After gene transfer, expression of hHO-1 was only detected in the ischemic heart treated with vigilant hHO-1 plasmids. Masson trichrome staining showed significantly fewer fibrotic areas in vigilant hHO-1 plasmids-treated mice compared with saline control (43.0%+/-4.8% versus 62.5%+/-3.3%, P<0.01). The reduction of interstitial fibrosis is accompanied by an increase in myocardial hHO-1 expression in peri-infarct border areas, concomitant with higher Bcl-2 levels and lower Bax, Bak, and caspase 3 levels in the ischemic myocardium compared with saline control. By use of a cardiac catheter, heart from vigilant hHO-1 plasmids-treated mice showed improved recovery of contractile and diastolic performance after myocardial infarction compared with saline control. This study documents the beneficial regulation and therapeutic potential of vigilant plasmid-mediated hHO-1 gene transfer. This novel gene transfer strategy can provide cardiac-specific protection from future repeated bouts of ischemic injury.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BAK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GAL4 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HMOX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase (Decyclizing),
http://linkedlifedata.com/resource/pubmed/chemical/Heme Oxygenase-1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2 Homologous Antagonist-Killer...,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1524-4563
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
746-51
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14981066-Apoptosis,
pubmed-meshheading:14981066-Binding Sites,
pubmed-meshheading:14981066-Biosensing Techniques,
pubmed-meshheading:14981066-Caspase 3,
pubmed-meshheading:14981066-Caspases,
pubmed-meshheading:14981066-Cell Hypoxia,
pubmed-meshheading:14981066-DNA-Binding Proteins,
pubmed-meshheading:14981066-Endomyocardial Fibrosis,
pubmed-meshheading:14981066-Gene Expression Regulation,
pubmed-meshheading:14981066-Gene Therapy,
pubmed-meshheading:14981066-Genes, Synthetic,
pubmed-meshheading:14981066-Genetic Vectors,
pubmed-meshheading:14981066-Heme Oxygenase (Decyclizing),
pubmed-meshheading:14981066-Heme Oxygenase-1,
pubmed-meshheading:14981066-Humans,
pubmed-meshheading:14981066-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:14981066-Membrane Proteins,
pubmed-meshheading:14981066-Myocardial Infarction,
pubmed-meshheading:14981066-Myosin Light Chains,
pubmed-meshheading:14981066-Plasmids,
pubmed-meshheading:14981066-Protein Structure, Tertiary,
pubmed-meshheading:14981066-Proto-Oncogene Proteins,
pubmed-meshheading:14981066-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:14981066-Regulatory Sequences, Nucleic Acid,
pubmed-meshheading:14981066-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:14981066-TATA Box,
pubmed-meshheading:14981066-Transcription Factors,
pubmed-meshheading:14981066-Transcriptional Activation,
pubmed-meshheading:14981066-bcl-2 Homologous Antagonist-Killer Protein,
pubmed-meshheading:14981066-bcl-2-Associated X Protein
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pubmed:year |
2004
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pubmed:articleTitle |
Protection from ischemic heart injury by a vigilant heme oxygenase-1 plasmid system.
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pubmed:affiliation |
Department of Pediatrics, College of Medicine and All Children's Hospital Research Institute, University of South Florida, St. Petersburg, Fla, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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