Angiotensin II type 1 receptor participates in extracellular matrix production in the late stage of remodeling after vascular injury.
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.
Eto
Hideyuki
H
The First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Biro
Sadatoshi
S
Miyata
Masaaki
M
Kaieda
Hiroshi
H
Obata
Hachiro
H
Kihara
Takashi
T
Orihara
Koji
K
Tei
Chuwa
C
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*
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D003094:Collagen; D010196:Pancreatic Elastase