Role of nuclear factor-kappaB in a rat model of vascular injury.
In this study we have investigated the relationship between neointima formation and NF-kappaB activation in a model of endothelial denudation of rat carotid artery (balloon angioplasty) using the antioxidant pyrrolidine dithiocarbamate as inhibitor of NF-kappaB activation. Furthermore, we have correlated NF-kappaB activation to the expression of inducible isoforms of both nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in injured carotids. In control group a significant proliferation of neointima was observed 14 days after balloon angioplasty, which was correlated to an increase of NF-kappaB/DNA binding activity as well as p50/p65 nuclear levels compared to those observed in the carotids from naive or sham-operated rats. Furthermore, NF-kappaB activation was correlated to increased iNOS and COX-2, but not beta-actin, protein expression. Treatment of rats for 14 days with the antioxidant agent pyrrolidine dithiocarbamate (50, 100, 200 mg/kg per os and day) caused a significant inhibition of all the parameters assayed, except beta-actin protein expression. These results indicate that prevention of NF-kappaB activation may lead to the inhibition of neointima formation and suggest that antioxidant agents may have therapeutic relevance for the prevention of human restenosis.
Ialenti
A
A
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Ianaro
A
A
Maffia
P
P
Carnuccio
R
R
D'Acquisto
F
F
Maiello
F M
FM
Di Rosa
M
M
D000800:Angioplasty, Balloon; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000293:injuries*; D015153:Blotting, Western; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D051546:Cyclooxygenase 2; D003720:Densitometry; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011233:Precipitin Tests; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013859:Thiocarbamates / Q000494:pharmacology
D000975:Antioxidants; D007527:Isoenzymes; D016328:NF-kappa B; D018809:Proliferating Cell Nuclear Antigen; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases