Source:http://linkedlifedata.com/resource/pubmed/id/16614302
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
2006-5-26
|
| pubmed:abstractText |
One intrinsic abnormality of pulmonary artery smooth muscle cells (PA-SMCs) in human idiopathic pulmonary hypertension (iPH) is an exaggerated proliferative response to internalized serotonin (5-HT) caused by increased expression of the 5-HT transporter (5-HTT). To investigate whether 5-HTT overexpression in PA-SMCs is sufficient to produce PH, we generated transgenic mice overexpressing 5-HTT under the control of the SM22 promoter. Studies in SM22-LacZ(+) mice showed that the transgene was expressed predominantly in SMCs of pulmonary and systemic vessels. Compared with wild-type mice, SM22-5-HTT(+) mice exhibited a 3- to 4-fold increase in lung 5-HTT mRNA and protein, together with increased lung 5-HT uptake activity, but no changes in platelet 5-HTT activity or blood 5-HT levels. At 8 weeks of age, SM22-5-HTT(+) mice exhibited PH, with marked increases in right ventricular systolic pressure (RVSP), right ventricle/left ventricle+septum ratio, and muscularization of distal pulmonary vessels, but no changes in systemic arterial pressure. PH worsened with age. Except a marked decrease in Kv channels, no changes in the lung expression of mediators of pulmonary vascular remodeling were observed in SM22-5-HTT(+) mice. Compared with wild-type mice, SM22-5-HTT(+) mice showed depressed hypoxic pulmonary vasoconstriction contrasting with greater severity of hypoxia- or monocrotaline-induced PH. These results show that increased 5-HTT expression in PA-SMCs, to a level close to that found in human iPH, lead to PH in mice. They further support a central role for 5-HTT in the pathogenesis of PH, making 5-HTT a potential therapeutic target.
|
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
1524-4571
|
| pubmed:author |
pubmed-author:AdnotSergeS,
pubmed-author:Barlier-MurAnne-MarieAM,
pubmed-author:EddahibiSaadiaS,
pubmed-author:GuignabertChristopheC,
pubmed-author:HamonMichelM,
pubmed-author:HanounNaïmaN,
pubmed-author:IzikkiMohamedM,
pubmed-author:LiZhenlinZ,
pubmed-author:RodmanDavidD,
pubmed-author:TuLy IengLI,
pubmed-author:ZadiguePatriciaP
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
26
|
| pubmed:volume |
98
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1323-30
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:16614302-Acute Disease,
pubmed-meshheading:16614302-Animals,
pubmed-meshheading:16614302-Anoxia,
pubmed-meshheading:16614302-Blood Pressure,
pubmed-meshheading:16614302-Blood Vessels,
pubmed-meshheading:16614302-Humans,
pubmed-meshheading:16614302-Hydroxyindoleacetic Acid,
pubmed-meshheading:16614302-Hypertension, Pulmonary,
pubmed-meshheading:16614302-Lung,
pubmed-meshheading:16614302-Mice,
pubmed-meshheading:16614302-Mice, Transgenic,
pubmed-meshheading:16614302-Monocrotaline,
pubmed-meshheading:16614302-Muscle, Smooth, Vascular,
pubmed-meshheading:16614302-Pulmonary Artery,
pubmed-meshheading:16614302-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:16614302-Tissue Distribution,
pubmed-meshheading:16614302-Transgenes,
pubmed-meshheading:16614302-Vasoconstriction,
pubmed-meshheading:16614302-Ventricular Function, Right
|
| pubmed:year |
2006
|
| pubmed:articleTitle |
Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth muscle develop pulmonary hypertension.
|
| pubmed:affiliation |
INSERM U651, Département de Physiologie, Hôpital H. Mondor, AP-HP, Créteil, France.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|