title: A selective peroxisome proliferator-activated receptor-β/δ agonist attenuates neointimal hyperplasia after wire-mediated arterial injury.
abstract: BACKGROUND
  Neointimal hyperplasia after the percutaneous coronary intervention is still a clinically serious problem, associated with the risk of thrombosis due to delayed reendothelization. Peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) belongs to a family of ligand-activated transcription factors.
  
  
  OBJECTIVE
  In this study, we investigated the effects of GW-0742, a synthetic high-affinity PPAR-β/δ agonist, on neointimal hyperplasia after arterial injury. Using C57BL/6J mice, we made a wire-injury model and intraperitoneally injected GW-0742 or vehicle once a day. The arteries were harvested for pathological and molecular analysis on day 14 after injury. In vitro, vascular smooth muscle cells (VSMCs), macrophages and human umbilical vein endothelial cells (HUVECs) were cultured, and GW-0742 effects on the cells proliferation were measured.
  
  
  RESULTS
  The vehicle-treated injured arteries showed significantly thickened intima, while GW-0742 suppressed it. GW-0742 significantly suppressed IL-6 protein production, the expression of proliferating cell nuclear antigen in the neointima and enhanced CD31 expression. In vitro, GW-0742 attenuated VSMC proliferation triggered by cytokines or macrophages. The drug also induced endothelial regeneration after denudation injury.
  
  
  CONCLUSIONS
  The data suggest that the PPAR-β/δ agonist is effective for atten- uation of neointimal hyperplasia by suppressing VSMC proliferation and accelerating reendothelization.
authors.affiliation: Tokyo Medical and Dental University, Department of Cardiovascular Medicine, Tokyo, Japan.
authors.forename: Rikuta
authors.initials: R
authors.lastname: Hamaya
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Naho
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima / Q000473:pathology / Q000517:prevention & control*; D047494:PPAR delta / Q000819:agonists*; D048068:PPAR-beta / Q000819:agonists*; D012038:Regeneration / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D010636:Phenols; D013438:Sulfhydryl Compounds
chemical_list: D016207:Cytokines; D047494:PPAR delta; D048068:PPAR-beta; D013844:Thiazoles; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds