Source:http://linkedlifedata.com/resource/pubmed/id/19451898
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
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| pubmed:dateCreated |
2009-7-29
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| 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.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 4,
http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone
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| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1530-0307
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
89
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
887-902
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| pubmed:meshHeading |
pubmed-meshheading:19451898-Angiotensin II,
pubmed-meshheading:19451898-Animals,
pubmed-meshheading:19451898-Aorta, Thoracic,
pubmed-meshheading:19451898-Blood Pressure,
pubmed-meshheading:19451898-Cell Survival,
pubmed-meshheading:19451898-Cells, Cultured,
pubmed-meshheading:19451898-Disease Models, Animal,
pubmed-meshheading:19451898-Gene Expression,
pubmed-meshheading:19451898-Gene Silencing,
pubmed-meshheading:19451898-Hypoglycemic Agents,
pubmed-meshheading:19451898-Male,
pubmed-meshheading:19451898-Muscle, Smooth, Vascular,
pubmed-meshheading:19451898-Myocytes, Smooth Muscle,
pubmed-meshheading:19451898-PPAR gamma,
pubmed-meshheading:19451898-RNA, Small Interfering,
pubmed-meshheading:19451898-RNA Interference,
pubmed-meshheading:19451898-Rats,
pubmed-meshheading:19451898-Rats, Sprague-Dawley,
pubmed-meshheading:19451898-Signal Transduction,
pubmed-meshheading:19451898-Thiazolidinediones,
pubmed-meshheading:19451898-Toll-Like Receptor 4,
pubmed-meshheading:19451898-Vasculitis
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| pubmed:year |
2009
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| pubmed:articleTitle |
PPARgamma agonist, rosiglitazone, regulates angiotensin II-induced vascular inflammation through the TLR4-dependent signaling pathway.
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| pubmed:affiliation |
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, PR China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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