Linked Life Data

21205918

Source:http://linkedlifedata.com/resource/pubmed/id/21205918

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-3-23
pubmed:abstractText
Calcific aortic valve stenosis (CAS) is the most frequent heart valve disease in the elderly, accompanied by valve calcification. Tumor necrosis factor-? (TNF-?), a pleiotropic cytokine secreted mainly from macrophages, has been detected in human calcified valves. However, the role of TNF-? in valve calcification remains unclear. To clarify whether TNF-? accelerates the calcification of aortic valves, we investigated the effect of TNF-? on human aortic valve interstitial cells (HAVICs) obtained from patients with CAS (CAS group) and with aortic regurgitation or aortic dissection having a noncalcified aortic valve (control group). HAVICs (2 × 10(4)) were cultured in a 12-well dish in Dulbecco's modified Eagle's medium with 10% fetal bovine serum. The medium containing TNF-? (30 ng/ml) was replenished every 3 days after the cells reached confluence. TNF-? significantly accelerated the calcification and alkaline phosphatase (ALP) activity of HAVICs from CAS but not the control group after 12 days of culture. Furthermore, gene expression of calcigenic markers, ALP, bone morphogenetic protein 2 (BMP2), and distal-less homeobox 5 (Dlx5) were significantly increased after 6 days of TNF-? treatment in the CAS group but not the control group. Dorsomorphin, an inhibitor of mothers against decapentaplegic homologs (Smads) 1/5/8 phosphorylation, significantly inhibited the enhancement of TNF-?-induced calcification, ALP activity, Smad phosphorylation, and Dlx5 gene expression of HAVICs from the CAS group. These results suggest that HAVICs from the CAS group have greater sensitivity to TNF-?, which accelerates the calcification of aortic valves via the BMP2-Dlx5 pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
337
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16-23
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Tumor necrosis factor-? accelerates the calcification of human aortic valve interstitial cells obtained from patients with calcific aortic valve stenosis via the BMP2-Dlx5 pathway.
pubmed:affiliation
Department of Pharmacology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't