title: Role of NF-κβ and oxidative pathways in atherosclerosis: cross-talk between dyslipidemia and candesartan.
abstract: OBJECTIVE
  The objective of this study is to assess the effect of the candesartan on the progression of atherosclerosis through the downregulation of NF-κβ and interference with oxidative pathway.
  
  
  METHODS
  Twenty-four rabbits were assigned to three groups: control group fed normal diet; induced untreated group fed 1% cholesterol diet; and treated candesartan group also fed 1% cholesterol diet. Plasma lipid profiles were measured, and ELISA for plasma cytokines and chemokine was performed. Analyses of NF-κβ and VCAM-1 were performed using Western blotting with RT-PCR for NF-κB activity at mRNA. Doppler ultrasound was used to evaluate aortic intima-media thickness, and atheroma was detected by H&E staining. Immunofluorescent staining was performed to confirm accumulation of monocytes and PMNs.
  
  
  RESULTS
  Candesartan markedly reduced the levels of the plasma lipid profile including total cholesterol [TC], triglycerides [TG], and LDL-C, while significantly elevating levels in the plasma HDL-C, in addition to reducing cytokine (TNF-α, IL-6, IL-1β) and chemokine levels (MCP-1). Also, it decreased the aortic malondialdehyde (MDA) concentration and elevated the aortic glutathione (GSH) level compared with untreated animals (P < 0.05). The triplex Doppler ultrasound study confirmed that the candesartan attenuated intima-media thickness at 6 months of study. All candesartan-treated rabbits showed significantly attenuated atherosclerosis lesions with reduced accumulation of monocytes and had significantly reduced VCAM-1 expression and NF-κβ activity.
  
  
  CONCLUSIONS
  Candesartan retards the progression of atherosclerosis via interference with NF-κβ and oxidative pathways.
authors.affiliation: Departments of Pharmacology and Therapeutics, College of Medicine, Kufa University, Najaf, Iraq.
authors.forename: Najah R
authors.initials: NR
authors.lastname: Hadi
authors.forename: Nasser Ghaly
authors.initials: NG
authors.lastname: Yousif
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Abdulzahra
authors.forename: Bassim I
authors.initials: BI
authors.lastname: Mohammad
authors.forename: Fadhil G
authors.initials: FG
authors.lastname: Al-Amran
authors.forename: Murooge L
authors.initials: ML
authors.lastname: Majeed
authors.forename: Maitham G
authors.initials: MG
authors.lastname: Yousif
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D002465:Cell Movement / Q000187:drug effects; D018925:Chemokines / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D050171:Dyslipidemias / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D010084:Oxidation-Reduction; D011817:Rabbits; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018925:Chemokines; D016207:Cytokines; D008055:Lipids; D016328:NF-kappa B; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; C081643:candesartan
keywords: Atherosclerosis; Candesartan; NF-κβ; Oxidative stress