Role of NF‐κβ and oxidative pathways in atherosclerosis: Cross‐talk between dyslipidemia and candesarta
الباحث الأول:
Najah R Hadi
الباحثين الآخرين:
Nasser Ghaly Yousif, Mohammed S Abdulzahra, Bassim I Mohammad, Fadhil G al‐amran, Murooge L Majeed, Maitham G Yousif
المجلة:
Cardiovascular therapeutics
تاريخ النشر:
None
مختصر البحث:
Summary
Purpose
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…
Summary
Purpose
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.
Conclusion
Candesartan retards the progression of atherosclerosis via interference with NF‐κβ and oxidative pathways.
