PMID- 25975094
OWN - NLM
STAT- MEDLINE
DCOM- 20150602
LR  - 20150515
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 70
IP  - 1
DP  - 2015 Jan
TI  - Therapeutic effects of the soluble epoxide hydrolase (sEH) inhibitor AUDA on 
      atherosclerotic diseases.
PG  - 24-8
AB  - In this study, we aimed to detect the effects of the soluble epoxide hydrolase 
      (sEH) inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) on 
      atherosclerotic diseases and to explore its mechanism. The atherosclerosis animal 
      model was constructed by ApoE-/- mice. To determine the optimal therapeutic 
      concentration of AUDA, different concentrations of AUDA were infused into ApoE-/- 
      mice, with controls receiving infusions of normal saline alone. Mouse body weight 
      and serum total cholesterol, triglyceride, LDL and HDL levels were measured. The 
      western blotting (WB) method was used to detect the expression of TLR4 and NFKB 
      in the aortic wall of the AUDA-treated and control mice. After the animals were 
      sacrificed, we performed Oil Red O staining of the aortic sinus atherosclerotic 
      plaque area followed by quantitative analysis of the aortic atherosclerotic 
      plaque size and the percentage of lumen area in the two groups of mice. The 
      expression levels of inflammatory cytokines, adhesion molecules and chemokines in 
      the AUDA group were significantly decreased compared to the saline-treatment 
      group (P < 0.05). The optimal AUDA concentration was found to be 0.35 ml/mg. AUDA 
      significantly inhibited the expression of TLR4 and NFkappaB in ApoE-/- mouse aortas 
      and reduced the aortic sinus plaque area of the ApoE-/- mouse group (P < 0.05). 
      In conclusion, AUDA can regulate blood lipid balance, which may be one of the 
      mechanisms for its protective effects on the cardiovascular system.
FAU - Zhang, Juan
AU  - Zhang J
FAU - Liu, Yu-Sheng
AU  - Liu YS
FAU - Lu, Qing-Hua
AU  - Lu QH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (12-(3-adamantan-1-ylureido)dodecanoic acid)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lauric Acids)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/therapeutic use
MH  - Animals
MH  - Aorta, Thoracic/drug effects/metabolism
MH  - Apolipoproteins E/genetics/metabolism
MH  - Atherosclerosis/*drug therapy
MH  - Cytokines/biosynthesis
MH  - Enzyme Inhibitors/*therapeutic use
MH  - Epoxide Hydrolases/*antagonists & inhibitors
MH  - In Vitro Techniques
MH  - Lauric Acids/*therapeutic use
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Plaque, Atherosclerotic/drug therapy/metabolism
MH  - Toll-Like Receptor 4/metabolism
EDAT- 2015/05/16 06:00
MHDA- 2015/06/03 06:00
CRDT- 2015/05/16 06:00
PHST- 2015/05/16 06:00 [entrez]
PHST- 2015/05/16 06:00 [pubmed]
PHST- 2015/06/03 06:00 [medline]
PST - ppublish
SO  - Pharmazie. 2015 Jan;70(1):24-8.