| pubmed-article:19451898 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0021368 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C1801960 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0003018 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0243192 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0166417 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0289313 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0086982 | lld:lifeskim |
| pubmed-article:19451898 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:19451898 | pubmed:issue | 8 | lld:pubmed |
| pubmed-article:19451898 | pubmed:dateCreated | 2009-7-29 | lld:pubmed |
| pubmed-article:19451898 | pubmed:abstractText | Atherosclerosis is increasingly recognized as a chronic inflammatory disease. Angiotensin II (Ang II) is a critical factor in inflammatory responses, so as to promote the pathogenesis of atherosclerosis. Toll-like receptor 4 (TLR4) activates signaling pathways leading to the expression of pro-inflammatory cytokines implicated in the etiology of atherosclerosis. Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists are considered to be important in modulating vascular inflammation and atherosclerosis. Herein, we investigated the modulatory effects of rosiglitazone on Ang II-mediated inflammatory responses both in vivo and in vitro. We also examined whether TLR4-dependent signaling pathway was involved in the inhibitory effects of rosiglitazone on Ang II-induced pro-inflammatory responses in vascular smooth muscle cells (VSMCs). Male Sprague-Dawley rats received Ang II by subcutaneous infusion and/or rosiglitazone per os for 7 days. Systolic blood pressure rise in Ang II-infused rats was attenuated by rosiglitazone. Rosiglitazone also reduced Ang II-induced generation of pro-inflammatory mediators (TLR4, matrix metalloproteinase-9 and tumor necrosis factor-alpha), but enhanced production of anti-inflammatory mediators (PPARgamma and 6-keto-PGF(1alpha)) both in vivo and in vitro. Furthermore, treatment of VSMCs with both the TLR4 inhibitor and TLR4 small-interfering RNA (siRNA) showed that the modulatory effects of rosiglitazone on Ang II-mediated inflammatory responses in VSMCs were related to TLR4. Treatment of the cells with rosiglitazone had little effect on Ang II receptors expression (AT1 and AT2), but downregulated AT1-dependent ERK1/2 activation. Then, treatment of VSMCs with TLR4 siRNA, interferon-gamma-inducible protein 10 (IP-10) siRNA and with the special protein kinase C (PKC) inhibitor further revealed that the signaling pathway (TLR4/IP-10/PKC/NF-kappaB) was involved in the inhibitory effects of rosiglitazone on Ang II-induced pro-inflammatory responses in VSMCs. In conclusion, TLR4 may be a drug target involved in the ameliorative effects of PPARgamma agonist, rosiglitazone, on Ang II-mediated inflammatory responses in VSMCs. Moreover, rosiglitazone exerts its anti-inflammatory effect by interfering with the TLR4-dependent signaling pathway (ERK1/2/TLR4/IP-10/PKC/NF-kappaB) to prevent and treat atherosclerotic diseases. | lld:pubmed |
| pubmed-article:19451898 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19451898 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19451898 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19451898 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:19451898 | pubmed:issn | 1530-0307 | lld:pubmed |
| pubmed-article:19451898 | pubmed:author | pubmed-author:UkeE TET | lld:pubmed |
| pubmed-article:19451898 | pubmed:author | pubmed-author:LiuNaN | lld:pubmed |
| pubmed-article:19451898 | pubmed:author | pubmed-author:LiuJuntianJ | lld:pubmed |
| pubmed-article:19451898 | pubmed:author | pubmed-author:JiYuanyuanY | lld:pubmed |
| pubmed-article:19451898 | pubmed:author | pubmed-author:ZhidongWangW | lld:pubmed |
| pubmed-article:19451898 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19451898 | pubmed:volume | 89 | lld:pubmed |
| pubmed-article:19451898 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19451898 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19451898 | pubmed:pagination | 887-902 | lld:pubmed |
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| pubmed-article:19451898 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19451898 | pubmed:articleTitle | PPARgamma agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway. | lld:pubmed |
| pubmed-article:19451898 | pubmed:affiliation | Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China. | lld:pubmed |
| pubmed-article:19451898 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19451898 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:19451898 | lld:pubmed |
