Linked Life Data

20977376

Source:http://linkedlifedata.com/resource/pubmed/id/20977376

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-10-27
pubmed:abstractText
This study sought to determine if antisense oligodeoxynucleotides would inhibit E-selectin expression, which mediates leukocyte adhesion on endothelial cells, otherwise induced by in vivo endotoxin challenge. Six antisense phosphorothioate oligodeoxynucleotides calculated to bind porcine E-selectin mRNA were tested in porcine aortic endothelial cells. One, ISIS9481, exerted significant inhibition of E-selectin expression induced by tumor necrosis factor-??+?endotoxin [lipopolysaccharide (LPS)]. Pigs were challenged with LPS (10??g/kg) and treated with ISIS9481 (10?mg/kg) (n?=?6). Two control groups were used, an antisense inactive in porcine aortic endothelial cells (n?=?6) and saline (n?=?5), and were combined as control (C?=?11). Control pigs challenged with LPS expressed E-selectin in heart, lung, kidneys, and liver, whereas antisense-treated pigs expressed little E-selectin in these tissues. Cardiovascular data indicated that antisense treatment attenuated pathophysiological alterations induced by LPS. Specifically, in control pigs, LPS reduced cardiac output 32% from baseline, increased pulmonary (+116%) and systemic vascular resistances (+16%), and generated neutropenia (from 51,000 at basal to 18,000 polymorphonuclear neutrophils (PMN)/?L after LPS). In antisense-treated pigs, cardiac output decreased only 18%, pulmonary vascular resistance remained unchanged, whereas systemic vascular resistance decreased compared with basal values (-37%). PMN counts remained at 45,000-54,000/?L at 3-4 hours after LPS. These data demonstrate that antisense oligodeoxynucleotides, designed and tested in vitro to interact with 1 gene product, can be developed as either therapeutics or experimental tools in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1557-8526
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
253-61
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Targeting host E-selectin expression by antisense oligodeoxynucleotides as potential antiendotoxin therapy in vivo.
pubmed:affiliation
Department of Cardiology, Cooper University Hospital , Camden, NJ, USA. goldfard@umdnj.edu
pubmed:publicationType
Journal Article