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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1997-8-21
|
| pubmed:abstractText |
Human kallistatin, or human tissue kallikrein-binding protein (HKBP), is a serine proteinase inhibitor (serpin). Transgenic mice overexpressing rat kallikrein-binding protein are hypotensive. To elucidate therapeutic potentials of kallistatin in hypertension, the human kallistatin gene in an adenoviral vector was directly introduced into spontaneously hypertensive rats (SHR) through portal vein injection. The kallistatin cDNA construct (RSV-cHKBP) under the promoter control of Rous sarcoma virus 3' long terminal repeat (LTR) was incorporated into adenovirus (Ad.RSV-cHKBP). Recombinant kallistatin in 293 cells transfected with RSV-cHKBP or Ad.RSV-cHKBP was measured by ELISA and by its complex formation with tissue kallikrein. A single intraportal vein injection of Ad.RSV-cHKBP at a dose of 8 x 10(10) pfu results in a significant reduction of blood pressure of SHR for 4 weeks. Human kallistatin mRNA was detected in the liver, spleen, kidney, aorta, and lung of rats receiving gene delivery. Immunoreactive human kallistatin in rat serum was detected at the highest level 1 day post injection and at lesser amounts in rat tissues. This study shows that adenovirus harboring Ad.RSV-cHKBP produces functional kallistatin, and adenovirus-mediated transfer of the human kallistatin gene reduces blood pressures of SHR. The results suggest that kallistatin may function as a vasodilator in vivo and provide important information for a potential gene therapy approach to hypertension.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Kallikreins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Serpins,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/kallistatin
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
1043-0342
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
341-7
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9048201-Adenoviridae,
pubmed-meshheading:9048201-Animals,
pubmed-meshheading:9048201-Avian Sarcoma Viruses,
pubmed-meshheading:9048201-Blood Pressure,
pubmed-meshheading:9048201-Carrier Proteins,
pubmed-meshheading:9048201-Cell Line,
pubmed-meshheading:9048201-Gene Expression,
pubmed-meshheading:9048201-Genetic Vectors,
pubmed-meshheading:9048201-Humans,
pubmed-meshheading:9048201-Hypertension,
pubmed-meshheading:9048201-Kallikreins,
pubmed-meshheading:9048201-Plasmids,
pubmed-meshheading:9048201-Rats,
pubmed-meshheading:9048201-Rats, Inbred SHR,
pubmed-meshheading:9048201-Recombinant Proteins,
pubmed-meshheading:9048201-Serine Proteinase Inhibitors,
pubmed-meshheading:9048201-Serpins,
pubmed-meshheading:9048201-Transfection,
pubmed-meshheading:9048201-Vasodilator Agents
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Adenovirus-mediated delivery of human kallistatin gene reduces blood pressure of spontaneously hypertensive rats.
|
| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425-2211, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|