N-acetylcysteine inhibited nuclear factor-kappaB expression and the intimal hyperplasia in rat carotid arterial injury.
Neointima formation associated with vascular restenosis is a complex local inflammatory process actively involving the vascular smooth muscle cell (SMC) proliferation. Nuclear factor-kappaB (NF-kappaB) is a transactivator of a diverse group of genes whose activation has been strongly associated with the cellular response to inflammation. Since anti-oxidant N-acetylcysteine (NAC) inhibit NF-kappaB activity in vascular SMC in vitro, we examined the in vivo effect of the NAC on balloon-induced neointimal formation in the carotid artery of rats. Sprague-Dawley rats underwent balloon dilatation injury of the left carotid artery to induce neointimal formation. One group of these rats (n = 9) were treated with daily intraperitoneal injection of NAC (200 mg kg(-1)) for 14 consecutive days, whereas the control group (n = 9) was treated with saline. Fourteen days after the injury, the left carotid arteries were removed and analyzed under microscope. Several rats underwent the same treatment as above and were sacrificed three days after injury for immunohistochemistry and Western blot studies. A morphometric analysis revealed that there were significant differences in intima/media ratio between the two groups. Immunohistochemical and Western blotting studies demonstrated that NAC suppressed the injury-induced NF-kappaB activity in the medial SMC layer. Treatment with NAC suppresses vascular NF-kappaB activation and this inhibition reduced the pathological thickening of the arterial wall. The NF-kappaB pathway, therefore, represents an attractive therapeutic target for strategies to prevent vascular restenosis.
Hayashi
K
K
Department of Neurosurgery, Nagasaki University School of Medicine, Japan. kentahayashi-nsu@umin.ac.jp
Takahata
H
H
Kitagawa
N
N
Kitange
G
G
Kaminogo
M
M
Shibata
S
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D023903:Coronary Restenosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006965:Hyperplasia / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects* / Q000293:injuries / Q000473:pathology
D016207:Cytokines; D016166:Free Radical Scavengers; D016328:NF-kappa B; D000111:Acetylcysteine