Source:http://linkedlifedata.com/resource/pubmed/id/12920239
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2003-8-15
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| pubmed:abstractText |
Nuclear factor-kappaB (NF-kappaB) plays a central role in myocardial ischemia-reperfusion (MI/R) injury. The inhibitory protein IkappaBalpha prevents its activation. We investigated the effects of adeno-associated viral vector-mediated IkappaBalpha gene transfer in MI/R injury. Male C57BL/6 mice were randomized to receive a recombinant adeno-associated virus (rAAV) encoding the gene for the NF-kappaB inhibitory protein IkappaBalpha (rAAV- IkappaBalpha) or the beta-galactosidase gene (a control and inert gene; rAAV-LacZ), both at a dose of 10(11) copies. Four weeks later anesthetized animals were subjected to total occlusion (45 minutes) of the left main coronary artery followed by 5 hours of reperfusion. MI/R produced a wide infarct size (IF/area-at-risk = 56 +/- 8%; IF/left ventricle = 44 +/- 5%) and tissue neutrophil infiltration, studied by means of elastase activity (area-at-risk = 2.5 +/- 0.4 micro g/gm tissue; infarct area = 2.9 +/- 0.6 micro g/gm tissue). Furthermore MI/R caused peak message for intercellular adhesion molecule-1 (ICAM-1) in the area-at-risk at 3 hours of reperfusion (1.2 +/- 0.4 relative amount of cardiac ICAM-1 mRNA). NF-kappaB activation was evident at 0.5 hours of reperfusion and reached its maximum increase at 2 hours of reperfusion. rAAV-IkappaBalpha injection reduced infarct size (IF/area-at-risk = 19 +/- 3%; IF/left ventricle = 10 +/- 2%; p < 0.001), blocked NF-kappaB activation, diminished cardiac ICAM-1 expression (0.4 +/- 0.02 relative amount of cardiac ICAM-1 mRNA; p < 0.001), and blunted leukocyte accumulation (area-at-risk = 0.6 +/- 0.05 micro g/gm tissue; infarct area = 0.4 +/- 0.02 micro g/gm tissue; p < 0.001). Our data indicate that rAAV-IkappaBalpha may be useful for MI/R gene therapy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Elastase,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/beta-Galactosidase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
0023-6837
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| pubmed:author |
pubmed-author:AdamoElena BEB,
pubmed-author:AltavillaDomenicaD,
pubmed-author:BellomoMariaM,
pubmed-author:DeodatoBarbaraB,
pubmed-author:GaleanoMariarosariaM,
pubmed-author:GiaccaMauroM,
pubmed-author:MariniHerbertH,
pubmed-author:MariniRolandoR,
pubmed-author:MinutoliLetteriaL,
pubmed-author:PassanitiMariaM,
pubmed-author:SeminaraPaoloP,
pubmed-author:SquadritoFrancescoF,
pubmed-author:SquadritoGiovanniG,
pubmed-author:VenutiFrancesco SFS
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| pubmed:issnType |
Print
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| pubmed:volume |
83
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1097-104
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:12920239-Adenoviridae,
pubmed-meshheading:12920239-Animals,
pubmed-meshheading:12920239-Blotting, Western,
pubmed-meshheading:12920239-DNA Primers,
pubmed-meshheading:12920239-Gene Therapy,
pubmed-meshheading:12920239-Gene Transfer Techniques,
pubmed-meshheading:12920239-Heart Ventricles,
pubmed-meshheading:12920239-I-kappa B Proteins,
pubmed-meshheading:12920239-Intercellular Adhesion Molecule-1,
pubmed-meshheading:12920239-Male,
pubmed-meshheading:12920239-Mice,
pubmed-meshheading:12920239-Mice, Inbred C57BL,
pubmed-meshheading:12920239-Myocardial Infarction,
pubmed-meshheading:12920239-Myocardial Reperfusion Injury,
pubmed-meshheading:12920239-NF-kappa B,
pubmed-meshheading:12920239-Pancreatic Elastase,
pubmed-meshheading:12920239-RNA, Messenger,
pubmed-meshheading:12920239-Transduction, Genetic,
pubmed-meshheading:12920239-beta-Galactosidase
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| pubmed:year |
2003
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| pubmed:articleTitle |
Gene transfer of IkappaBalpha limits infarct size in a mouse model of myocardial ischemia-reperfusion injury.
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| pubmed:affiliation |
Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy. Francesco.Squadrito@unime.it
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| pubmed:publicationType |
Journal Article
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