PMID- 26016366
OWN - NLM
STAT- MEDLINE
DCOM- 20150726
LR  - 20181202
IS  - 1000-6834 (Print)
IS  - 1000-6834 (Linking)
VI  - 30
IP  - 6
DP  - 2014 Nov
TI  - Stimulation of endothelial non-neuronal muscarinic receptor attenuates the 
      progression of atherosclerosis via inhibiting endothelial cells activation.
PG  - 549-59
AB  - OBJECTIVE: To investigate the effects of non-neuronal muscarinic receptors (NNMR) 
      stimulation on atherosclerosis and endothelial cells activation. METHODS: 
      Atherosclerosis model was established in ApoE-/- mice by a high fat diet for 7 
      weeks. During the experimental periods, animals were received a low (7 mg/kg/d) 
      or a high (21 mg/kg/d) dose of arecoline by gavage. At the termination of the 
      treatments, serum total cholesterol and NO levels were measured, and the aorta 
      morphology was analyzed by hematoxylin and eosin staining. The gene expression of 
      monocyte chemoattractant protein-1 (MCP-1) and adhesion molecules in the thoracic 
      aortas was determined by RT-PCR, and the MCP-1 protein expression and NF-kappaB 
      activity were detected by Western blot analysis. NO production, MCP-1 secretion 
      in cultured rat aortic endothelial cells (RAECs), and monocyte-endothelium 
      adhesion assay were also performed after arecoline treatments. RESULTS: Arecoline 
      efficiently decreased atherosclerotic plaque areas, increased serum nitric oxide 
      (NO) content, suppressed the mRNA and protein expression of MCP-1, and modulated 
      the IkappaB-alpha degradation and P65 phosphorylation in the aortae of ApoE-/- mice. 
      Furthermore, arecoline promoted NO production and suppressed MCP-1 secretion in 
      cultured RAECs after ox-LDL exposure, and either atropine or NG-nitro-L-arginine 
      methylester could abrogate these effects. Arecoline also significantly inhibited 
      the adherence of U937 monocytes to the ox-LDL injured human umbilical vein 
      endothelial cells, which could be abolished by atropine. CONCLUSION: Our results 
      indicate that arecoline attenuates the progression of atherosclerosis and 
      inhibits endothelial cells activation and adherence by stimulating endothelial 
      NNMR. These effects, at least in part, are due to its modulation on NF-kappaB 
      activity.
FAU - Zhou, Jing-Hong
AU  - Zhou JH
FAU - Pan, Zhi-Yuan
AU  - Pan ZY
FAU - Zhang, Yan-Fang
AU  - Zhang YF
FAU - Cui, Wen-Yu
AU  - Cui WY
FAU - Long, Chao-Liang
AU  - Long CL
FAU - Wang, Hai
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhongguo Ying Yong Sheng Li Xue Za Zhi
JT  - Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = 
      Chinese journal of applied physiology
JID - 9426407
RN  - 0 (Apolipoproteins E)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Rela protein, mouse)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (oxidized low density lipoprotein)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 2149-70-4 (Nitroarginine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 4ALN5933BH (Arecoline)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Apolipoproteins E
MH  - Arecoline/*pharmacology
MH  - Atherosclerosis/physiopathology/*prevention & control
MH  - Cell Adhesion Molecules/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Cholesterol/blood
MH  - Disease Progression
MH  - Endothelial Cells/*cytology/drug effects
MH  - Endothelium, Vascular
MH  - Human Umbilical Vein Endothelial Cells/cytology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Lipoproteins, LDL
MH  - Mice
MH  - Mice, Knockout
MH  - Monocytes/cytology
MH  - NF-KappaB Inhibitor alpha
MH  - Nitric Oxide/blood
MH  - Nitroarginine/pharmacology
MH  - Rats
MH  - Receptors, Muscarinic/*physiology
MH  - Transcription Factor RelA/metabolism
EDAT- 2015/05/29 06:00
MHDA- 2015/07/28 06:00
CRDT- 2015/05/29 06:00
PHST- 2015/05/29 06:00 [entrez]
PHST- 2015/05/29 06:00 [pubmed]
PHST- 2015/07/28 06:00 [medline]
PST - ppublish
SO  - Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2014 Nov;30(6):549-59.