title: Decreased neointimal extracellular matrix formation in RAGE-knockout mice after microvascular denudation.
abstract: OBJECTIVE
  To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model.
  
  
  METHODS
  Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, α-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant.
  
  
  RESULTS
  Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 μm(2) [n = 15) in the WT group compared with only 8.4 (*1000 μm(2) [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein.
  
  
  CONCLUSIONS
  RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.
authors.affiliation: Department of Diagnostic and Interventional Radiology, University of Tübingen, Hoppe-Seylerstr 3, 72076, Tübingen, Germany. gerd.groezinger@med.uni-tuebingen.de
authors.forename: Gerd
authors.initials: G
authors.lastname: Grözinger
authors.forename: Jörg
authors.initials: J
authors.lastname: Schmehl
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Bantleon
authors.forename: Rainer
authors.initials: R
authors.lastname: Kehlbach
authors.forename: Tarun
authors.initials: T
authors.lastname: Mehra
authors.forename: Claus
authors.initials: C
authors.lastname: Claussen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wiesinger
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005263:Femoral Artery / Q000601:surgery*; D051379:Mice; D018345:Mice, Knockout; D058426:Neointima; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014841:von Willebrand Factor; D003094:Collagen