title: Increased activity of nuclear factor-kappaB participates in cardiovascular remodeling induced by chronic inhibition of nitric oxide synthesis in rats.
abstract: BACKGROUND
  Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes [monocyte infiltration into coronary vessels, nuclear factor-kappaB (NF-kappaB) activation, and monocyte chemoattractant protein-1 expression] as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, no direct evidence for the importance of NF-kappaB in this process is known.
  
  
  RESULTS
  We examined the effect of a cis element decoy strategy to address the functional importance of NF-kappaB in the pathogenesis of cardiovascular remodeling. We found here that in vivo transfection of cis element decoy oligodeoxynucleotides against NF-kappaB to hearts prevented the L-NAME-induced early inflammation and subsequent coronary vascular medial thickening. In contrast, NF-kappaB decoy oligodeoxynucleotide transfection did not decrease the development of fibrosis, the expression of transforming growth factor-beta(1) mRNA, or systolic pressure overload induced by L-NAME administration.
  
  
  CONCLUSIONS
  The NF-kappaB system participates importantly in the development of early vascular inflammation and subsequent medial thickening but not in fibrogenesis in this model. The present study may provide a new aspect of how endothelium-derived NO contributes to anti-inflammatory and/or antiarteriosclerotic properties of the vascular endothelium in vivo.
authors.affiliation: Departments of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kitamoto
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: C
authors.initials: C
authors.lastname: Kataoka
authors.forename: M
authors.initials: M
authors.lastname: Koyanagi
authors.forename: M
authors.initials: M
authors.lastname: Katoh
authors.forename: H
authors.initials: H
authors.lastname: Shimokawa
authors.forename: R
authors.initials: R
authors.lastname: Morishita
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: K
authors.initials: K
authors.lastname: Sueishi
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013599:Systole; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics; D014657:Vasculitis / Q000139:chemically induced / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide