title: Inhibition of neointimal hyperplasia development by MCI-186 is correlated with downregulation of nuclear factor-kappaB pathway.
abstract: BACKGROUND
  Atherosclerosis is a progressing inflammatory response mediated by various signaling molecules among which nuclear factor kappaB (NF-kappaB) is thought to have a pivotal role. This study demonstrated the efficacy of antioxidant MCI-186 in preventing the progression of atherosclerosis by inhibiting signaling molecules such as NF-kappaB.
  
  
  RESULTS
  Balloon injury of intima was performed in the right common carotid artery of Japanese male white rabbits, which were then fed a 1% high cholesterol diet for 4 weeks, after assigning them to either the control (n=7) or MCI-186 (0.5 mg .kg(-1) . day(-1), n=7) group. Histological analysis revealed a reduction in neointimal thickness and lipid deposition in the subendothelial area of the MCI-186 group. Immunohistochemical analysis revealed attenuation of E-selectin expression, macrophage migration and proliferation of smooth muscle cells in the MCI-186 treated group. In in vitro studies, rabbit aorta smooth muscle cells were incubated with rIL-1betain either the presence or absence of MCI-186. MCI-186 significantly inhibited rIL-1beta-induced proliferation of smooth muscle cells from rabbit aorta, as well as the activation of NF-kappaB. Moreover, western blot analysis showed the inhibitory action of MCI-186 on the nuclear translocation of NF-kappaB in human umbilical vein endothelial cells under rIL-1betastimulation.
  
  
  CONCLUSIONS
  MCI-186 could provide a novel therapeutic strategy for atherosclerosis by inhibiting the NF-kappaB pathway.
authors.affiliation: Department of Surgery II, Faculty of Medicine, Kochi University, Nankoku, Japan.
authors.forename: Geethalakshmi
authors.initials: G
authors.lastname: Radhakrishnan
authors.forename: Ryoko
authors.initials: R
authors.lastname: Suzuki
authors.forename: Hironori
authors.initials: H
authors.lastname: Maeda
authors.forename: Morio
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hirose
authors.forename: Rajesh Katare
authors.initials: RK
authors.lastname: Gopalrao
authors.forename: Gang-Hang
authors.initials: GH
authors.lastname: Lee
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Parijatha
authors.initials: P
authors.lastname: Rao
authors.forename: Shiro
authors.initials: S
authors.lastname: Sasaguri
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D019040:E-Selectin / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006965:Hyperplasia; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D000975:Antioxidants; D019040:E-Selectin; D016166:Free Radical Scavengers; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D013481:Superoxides; D000072000:NF-KappaB Inhibitor alpha; D002784:Cholesterol; D000077553:Edaravone; D000983:Antipyrine