title: Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ mediates pioglitazone-reduced vascular lesion formation.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to decrease vascular lesion formation. However, the critical role of vascular smooth muscle cell (VSMC) PPARγ in vascular lesion formation following transplantation is not well understood. In this study, we investigated the role of VSMC PPARγ-mediated signaling in transplantation-associated vascular lesion formation.
  
  
  RESULTS
  Carotid arteries from smooth muscle cell-selective PPARγ knockout (SMPG KO) and wild-type mice were transplanted to CBA/CaJ recipient mice. The recipient mice received a control diet or pioglitazone-containing diet. Pioglitazone reduced vascular lesion formation in transplanted wild-type, but not in SMPG KO carotid arteries. Histological analysis suggested that PPARγ attenuates vascular lesion formation through antiinflammatory signaling, as evidenced by the increase of intimal inflammatory cells and tumor necrosis factor-α expression in SMPG KO allografts. Intravital microscopy revealed increased inflammatory cell rolling and attachment to endothelial cells in small blood vessels of SMPG KO mice following cytokine stimulation. SMPG KO mice, as shown by Western blotting, have elevated vascular cell adhesion molecule-1 (VCAM-1) expression. Furthermore, immunohistochemistry demonstrated SMPG KO allografts have increased VCAM-1.
  
  
  CONCLUSIONS
  Loss of PPARγ in VSMC promotes transplantation-associated vascular lesion formation through increased VCAM-1 expression. VSMC PPARγ also mediates pioglitazone-reduced vascular lesion formation.
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Hamblin
authors.forename: Lin
authors.initials: L
authors.lastname: Chang
authors.forename: Hengmin
authors.initials: H
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000818:Animals; D001167:Arteritis / Q000139:chemically induced* / Q000378:metabolism*; D002339:Carotid Arteries / Q000637:transplantation; D002448:Cell Adhesion / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D009000:Monocytes / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000077205:Pioglitazone; D015398:Signal Transduction / Q000502:physiology; D045162:Thiazolidinediones / Q000009:adverse effects*; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D000077205:Pioglitazone