Source:http://linkedlifedata.com/resource/pubmed/id/12070122
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
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| pubmed:dateCreated |
2002-6-18
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| pubmed:abstractText |
BACKGROUND: Neointima formation after arterial injury is associated with reduced vascular cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase (PKG), a major cGMP effector in vascular smooth muscle. We tested the effect of PKG overexpression on the neointimal response to vascular injury. Methods and Results- Infection of cultured rat aortic smooth muscle cells (RASMCs) with an adenoviral vector specifying a cGMP-independent, constitutively active PKG mutant (AdPKGcat) reduced serum-induced migration by 33% and increased serum-deprivation-induced apoptosis 2-fold (P<0.05 for both). Infection with wild-type PKG (AdPKG), in the absence of cGMP, did not affect migration or apoptosis. Two weeks after balloon-injured rat carotid arteries were infected with 1x 10(10) pfu AdPKGcat (n=12), AdPKG (n=8), or a control adenovirus (n=8), intima-to-media ratio was less in AdPKGcat-infected arteries than in AdPKG- or control adenovirus-infected vessels (0.26+/-0.06 versus 0.61+/-0.12 and 0.70+/-0.12, respectively, P<0.05 for both). Two weeks after intramural administration of 1.75x10(10) pfu AdPKGcat (n=8) or a control adenovirus (n=8) into porcine coronary arteries with in-stent restenosis, luminal diameter was greater in AdPKGcat-infected arteries than in control adenovirus-infected vessels (2.32+/-0.16 versus 1.81+/-0.13 mm, P=0.028), associated with reduced neointimal area (3.30+/-0.24 versus 4.15+/-0.13 mm(2), P=0.008), neointima-to-vessel area ratio (0.42+/-0.05 versus 0.58+/-0.04, P<0.05), and percent stenosis (45+/-6% versus 70+/-4%, P<0.05). CONCLUSIONS: Expression of a constitutively active PKG reduces neointima formation after balloon injury in rats and reduces coronary in-stent restenosis in pigs. PKGcat gene transfer may be a promising strategy for vasculoproliferative disorders.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
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| pubmed:issn |
1524-4539
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
18
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| pubmed:volume |
105
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2911-6
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:12070122-Adenoviridae,
pubmed-meshheading:12070122-Angioplasty, Balloon,
pubmed-meshheading:12070122-Animals,
pubmed-meshheading:12070122-Apoptosis,
pubmed-meshheading:12070122-Carotid Stenosis,
pubmed-meshheading:12070122-Cell Movement,
pubmed-meshheading:12070122-Cells, Cultured,
pubmed-meshheading:12070122-Coronary Restenosis,
pubmed-meshheading:12070122-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:12070122-Enzyme Activation,
pubmed-meshheading:12070122-Genetic Vectors,
pubmed-meshheading:12070122-Graft Occlusion, Vascular,
pubmed-meshheading:12070122-Kinetics,
pubmed-meshheading:12070122-Male,
pubmed-meshheading:12070122-Muscle, Smooth, Vascular,
pubmed-meshheading:12070122-Rats,
pubmed-meshheading:12070122-Rats, Wistar,
pubmed-meshheading:12070122-Stents,
pubmed-meshheading:12070122-Swine,
pubmed-meshheading:12070122-Transduction, Genetic
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| pubmed:year |
2002
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| pubmed:articleTitle |
Overexpression of a constitutively active protein kinase G mutant reduces neointima formation and in-stent restenosis.
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| pubmed:affiliation |
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, and the Cardiac Unit, University Hospital Gasthuisberg, University of Leuven, Belgium.
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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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