Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-12-30
pubmed:abstractText
Protease-activated receptor-2 (PAR2) is expressed in endothelial cells and mediates endothelium-dependent vasodilation. We hypothesized that PAR2 regulates tumor necrosis factor-alpha (TNF-?)-induced coronary arteriolar dysfunction in type 2 diabetic (db/db) mice. To test this, coronary arterioles from WT control, db/db, db/db mice treated with PAR2 antagonist FSLLRY-NH? (db/db+FSLLRY-NH?) and db/db mice null for TNF (db(TNF-)/db(TNF-)) were isolated and pressurized (60 cmH?O) without flow. Although vasodilation to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different among WT, db/db, db/db+FSLLRY-NH? and db(TNF-)/db(TNF-), endothelium-dependent acetylcholine (ACh)- and flow-mediated vasodilation were impaired in db/db mice but were enhanced in db(TNF-)/db(TNF-) mice and db/db mice treated with PAR2 antagonist. NOS inhibitor N (G)-nitro-L-arginine-methyl ester (L-NAME) significantly reduced ACh-induced dilation in WT, db(TNF-)/db(TNF-) and db/db+FSLLRY-NH?, but did not alter the vasodilation in db/db mice. In contrast, cyclooxygenase (COX) inhibitor indomethacin (Indo) did not alter ACh-induced vasodilation in these four groups of mice. PAR2-activating peptide (PAR2-AP, 2-Furoyl-LIGRLO-am)-induced dilation was higher in db/db mice than that in WT, db(TNF-)/db(TNF-) and db/db mice treated with PAR2 antagonist. These effects were abolished by denudation, or in the presence of L-NAME or Indo. Protein expressions of TNF-?, PAR2, gp91(phox) and p47(phox) in the heart and isolated coronary arterioles were higher in db/db mice compared to WT mice. Administration of PAR2 antagonist to db/db mice reduced protein expression of TNF-?, gp91(phox) and PAR2. Protein expression of gp91(phox) and p47(phox) was lower in db(TNF-)/db(TNF-) compared to db/db mice. These results indicate that PAR2 plays a pivotal role in endothelial dysfunction in type 2 diabetes by up-regulating the expression/production of TNF-? and activating NAD(P)H oxidase subunit p47(phox).
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-10330393, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-10471447, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-10689364, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-11356985, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-11440983, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-11692107, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-11786474, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-11934700, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12028372, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12415569, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12595345, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12600906, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12829649, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-12970102, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-14565830, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-14633513, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-15044683, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-15320742, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-16141401, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-16385082, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-16741160, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-16877369, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-16952995, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-17095716, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-17200442, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-17339845, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-17369094, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-17720772, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18431527, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18539754, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18600364, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18790831, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18836678, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-18983479, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19190953, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19363130, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19478208, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19812353, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19823892, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-19902320, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-20091314, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-20621692, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-8635215, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-8663011, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-9446822, http://linkedlifedata.com/resource/pubmed/commentcorrection/20972877-9806321
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1435-1803
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
111-23
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
More...