Linked Life Data

17038532

Source:http://linkedlifedata.com/resource/pubmed/id/17038532

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-7
pubmed:abstractText
Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) is emerging as an important regulator of vascular pathophysiology. Here, we demonstrate a novel role of RANKL as a vascular permeability factor and a critical role of endothelial nitric oxide synthase (eNOS) in RANKL-induced endothelial function. RANKL increased the vascular permeability and leukocyte infiltration in vivo and caused the breakdown of the blood-retinal barrier in wild-type mice but not in eNOS-deficient mice. In vitro, it increased endothelial permeability and reduced VE-cadherin-facilitated endothelial cell-cell junctions in a NO-dependent manner. RANKL also led to the activation of Akt and eNOS and to NO production in endothelial cells (ECs). These effects were suppressed by the inhibition of TRAF6, phosphoinositide 3'-kinase (PI3K), Akt, or NOS by genetic or pharmacologic means. Inhibition of the TRAF6-mediated NO pathway reduced EC migration and capillary-like tube formation in response to RANKL. Moreover, the effects of RANKL on ECs sprouting from the aorta, and neovessel formation in both the mouse Matrigel plug assay and corneal micropocket assay, were impaired in eNOS-deficient mice. These results demonstrate that RANKL promotes vascular permeability and angiogenesis by stimulating eNOS by a TRAF6-PI3K-Akt-dependent mechanism. These properties may be relevant to the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1495-502
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) increases vascular permeability: impaired permeability and angiogenesis in eNOS-deficient mice.
pubmed:affiliation
Department of Biochemistry, College of Sciences, Yonsei University, and Department of Ophthalmology, Seoul National University Hospital, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't