Source:http://linkedlifedata.com/resource/pubmed/id/14670847
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2004-2-6
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| pubmed:abstractText |
Cytochrome P450 (CYP) 4A1 has been characterized as the most efficient arachidonic acid omega-hydroxylase catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), a potent constrictor of the renal and cerebral microcirculation and a mitogen for smooth muscle cells. We constructed adenoviruses expressing the CYP4A1 cDNA or LacZ under the control of the smooth muscle cell-specific promoter SM22alpha (Ad-SM22-4A1 and Ad-SM22-nLacZ, respectively). Beta-galactosidase expression was detected in Ad-SM22-nLacZ-transduced vascular smooth muscle A7r5 and PAC1 cells, but not in Ad-SM22-nLacZ-transduced 3T3 fibroblasts or vascular endothelial cells. Likewise, CYP4A1 mRNA and protein were detected in Ad-SM22-4A1-transduced A7r5 and PAC1 cells. Ad-SM22-4A1-transduced A7r5 cells metabolized lauric acid to 12-hydroxy-lauric acid at a rate 5 times greater than that of cells transduced with Ad-SM22-nLacZ (4.79+/-1.77 versus 0.97+/-0.57 nmol 12-hydroxy lauric acid/10(6) cells per h). Smooth muscle-specific LacZ expression was also detected in microdissected renal interlobar arteries transduced with Ad-SM22-nLacZ. Arteries transduced with Ad-SM22-4A1 produced higher levels of 20-HETE (4.04+/-0.29 and 13.43+/-2.84 ng/mg protein in Ad-SM22-nLacZ-transduced and Ad-SM22-4A1-transduced arteries, respectively) and demonstrated a marked angiogenic activity measured as the total length of sprouting neovessels (12.63+/-3.66 mm in Ad-SM22-4A1-transduced vessels versus 1.79+/-0.89 mm in Ad-SM22-nLacZ-transduced vessels). This angiogenic activity represented endothelial cell sprouting and was fully blocked by treatment with HET0016, a selective inhibitor of CYP4A-catalyzed reactions. The inhibitory effect of HET0016 was reversed by addition of a 20-HETE agonist. We conclude that Ad-SM22-4A1 drives a smooth muscle-specific functional expression of CYP4A1 and demonstrates increased angiogenesis, presumably via increased production of 20-HETE.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/20-hydroxy-5,8,11,14-eicosatetraenoi...,
http://linkedlifedata.com/resource/pubmed/chemical/Amidines,
http://linkedlifedata.com/resource/pubmed/chemical/Cyp4a22 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Lauric Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Microfilament Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/N-hydroxy-N'-(4-butyl-2-methylphenyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Tagln protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/lauric acid,
http://linkedlifedata.com/resource/pubmed/chemical/transgelin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
1524-4571
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
6
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| pubmed:volume |
94
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
167-74
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| pubmed:dateRevised |
2011-11-10
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| pubmed:meshHeading |
pubmed-meshheading:14670847-3T3 Cells,
pubmed-meshheading:14670847-Adenoviridae,
pubmed-meshheading:14670847-Amidines,
pubmed-meshheading:14670847-Animals,
pubmed-meshheading:14670847-Cytochrome P-450 Enzyme System,
pubmed-meshheading:14670847-Enzyme Inhibitors,
pubmed-meshheading:14670847-Genetic Vectors,
pubmed-meshheading:14670847-Humans,
pubmed-meshheading:14670847-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:14670847-Lauric Acids,
pubmed-meshheading:14670847-Male,
pubmed-meshheading:14670847-Mice,
pubmed-meshheading:14670847-Microfilament Proteins,
pubmed-meshheading:14670847-Muscle, Smooth, Vascular,
pubmed-meshheading:14670847-Muscle Proteins,
pubmed-meshheading:14670847-Neovascularization, Physiologic,
pubmed-meshheading:14670847-Organ Specificity,
pubmed-meshheading:14670847-Promoter Regions, Genetic,
pubmed-meshheading:14670847-Rats,
pubmed-meshheading:14670847-Rats, Sprague-Dawley,
pubmed-meshheading:14670847-Renal Artery,
pubmed-meshheading:14670847-Transduction, Genetic,
pubmed-meshheading:14670847-Vascular Endothelial Growth Factor A
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| pubmed:year |
2004
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| pubmed:articleTitle |
Smooth muscle--specific expression of CYP4A1 induces endothelial sprouting in renal arterial microvessels.
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| pubmed:affiliation |
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, 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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