title: PPARγ attenuates intimal hyperplasia by inhibiting TLR4-mediated inflammation in vascular smooth muscle cells.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor γ (PPARγ) has been reported to attenuate intimal hyperplasia. This study aimed to test the hypothesis that PPARγ inhibits intimal hyperplasia through suppressing Toll-like receptor 4 (TLR4)-mediated inflammation in vascular smooth muscle cells.
  
  
  RESULTS
  TLR4(-/-) mice on a C57BL/6J background were used. Increased TLR4 and pro-inflammatory cytokines were observed in wire-injury-induced carotid neointima and in platelet-derived growth factor (PDGF)-activated vascular smooth muscle cells. The TLR4 deficiency protected the injured carotid from neointimal formation and impaired the cellular proliferation and migration in response to lipopolysaccharide and PDGF. Rosiglitazone attenuated intimal hyperplasia. Overexpression of PPARγ suppressed PDGF-induced proliferation and migration and inhibited TLR4-mediated inflammation in vascular smooth muscle cells, while PPARγ silencing exerted the opposite effect. Lipopolysaccharide counteracted the inhibitory effect of PPARγ on PDGF-induced proliferation and migration. Eritoran suppressed the proliferation and migration induced by PDGF and PPARγ silencing. Vascular smooth muscle cells derived from TLR4(-/-) mice showed impaired proliferation and migration upon PDGF activation and displayed no response to PPARγ manipulation.
  
  
  CONCLUSIONS
  PPARγ inhibits vascular smooth muscle cell proliferation and migration by suppressing TLR4-mediated inflammation and ultimately attenuates intimal hyperplasia after carotid injury.
authors: Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing 400042, PR China. zll197312@hotmail.com
authors: Li-Li
authors: LL
authors: Zhang
authors: Chang-Yue
authors: CY
authors: Gao
authors: Chuan-Qin
authors: CQ
authors: Fang
authors: Yan-Jiang
authors: YJ
authors: Wang
authors: Dong
authors: D
authors: Gao
authors: Guo-En
authors: GE
authors: Yao
authors: Jing
authors: J
authors: Xiang
authors: Jing-Zhou
authors: JZ
authors: Wang
authors: Jing-Cheng
authors: JC
authors: Li
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004187:Disaccharides / Q000494:pharmacology; D004195:Disease Models, Animal; D006965:Hyperplasia; D007249:Inflammation / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D034622:RNA Interference; D000077154:Rosiglitazone; D013403:Sugar Phosphates / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D017539:Tunica Intima / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D004187:Disaccharides; D008070:Lipopolysaccharides; D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D013403:Sugar Phosphates; D045162:Thiazolidinediones; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000077154:Rosiglitazone; C512420:eritoran