Linked Life Data

19801451

Source:http://linkedlifedata.com/resource/pubmed/id/19801451

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-11-25
pubmed:abstractText
Vascular remodeling and smooth muscle cell proliferation are hallmark pathogenic features of pulmonary artery hypertension (PAH). Alterations in the metabolism of l-arginine via arginase and nitric oxide synthase play a critical role in the endothelial dysfunction seen in PAH. l-arginine metabolism by arginase produces l-ornithine and urea. l-ornithine is a precursor for polyamine and proline synthesis, ultimately leading to an increase in cellular proliferation. Given the integral role of the smooth muscle layer in the pathogenesis of hypoxia-induced PAH, we hypothesized that hypoxia would increase cellular proliferation via arginase induction in human pulmonary artery smooth muscle cells (hPASMC). We found that arginase II mRNA and protein expression were significantly increased in cultured hPASMC exposed to 1% O(2) for 24 and 48 h, which coincided with an increase in arginase activity at 48 h. There were no hypoxia-induced changes in levels of arginase I mRNA or protein in cultured hPASMC. Exposure to hypoxia resulted in more than one and a half times as many viable cells after 120 h than normoxic exposure. The addition of the arginase inhibitor, S-(2-boronoethyl)-l-cysteine, completely prevented both the hypoxia-induced increase in arginase activity and proliferation in hPASMC. Furthermore, transfection of small interfering RNA (siRNA) targeting arginase II in hPASMC resulted in knockdown of arginase II protein levels and complete prevention of the hypoxia-induced cellular proliferation. These data support our hypothesis that hypoxia increases proliferation of hPASMC through the induction of arginase II.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1522-1504
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L1151-9
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Hypoxia promotes human pulmonary artery smooth muscle cell proliferation through induction of arginase.
pubmed:affiliation
Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, USA. bernadette.chen@nationwidechildrens.org
pubmed:publicationType
Journal Article