title: Angiotensin II type 1 receptor participates in extracellular matrix production in the late stage of remodeling after vascular injury.
abstract: OBJECTIVE
  Extracellular matrix (ECM) accumulation is important in restenosis after angioplasty. Underlying molecular mechanisms remain to be elucidated, especially in vivo. We investigated expression of angiotensin II type 1 receptor (ATR1) in a rat model for up to 24 weeks after vascular injury, and also the effect of an ATR1 antagonist on neointimal thickening and ECM production.
  
  
  RESULTS
  Carotid arteries of rats were injured with a balloon catheter and then removed at 2, 5, and 7 days and 2, 4, 8, 16, and 24 weeks after injury. Although ATR1 immunoreactivity was slightly detectable in smooth muscle cells (SMC) in the media of uninjured arteries, reactivity was strong in neointimal SMC even 24 weeks after injury. Western blotting demonstrated similar results. ATR1 mRNA also was upregulated in neointimal SMC even 24 weeks after injury, as indicated by RT-PCR and by in situ hybridization. Candesartan, an ATR1 antagonist, significantly inhibited histologically evident neointimal thickening and collagen and elastin accumulation at 8 weeks after injury whether given beginning 1 day before injury, 4 days after injury, or 7 days after injury.
  
  
  CONCLUSIONS
  ATR1 is upregulated in the late stage of remodeling after vascular injury and is important in ECM production.
authors.affiliation: The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Eto
authors.forename: Sadatoshi
authors.initials: S
authors.lastname: Biro
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaieda
authors.forename: Hachiro
authors.initials: H
authors.lastname: Obata
authors.forename: Takashi
authors.initials: T
authors.lastname: Kihara
authors.forename: Koji
authors.initials: K
authors.lastname: Orihara
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002339:Carotid Arteries; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization; D003094:Collagen / Q000032:analysis; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D023421:Models, Animal; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D010196:Pancreatic Elastase / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D003094:Collagen; D010196:Pancreatic Elastase