| WIN55212-2 ameliorates atherosclerosis associated with suppression of pro-inflammatory responses in ApoE-knockout mice. | |
| | |
MedLine Citation:
|
PMID: 20868672 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
|
The role of inflammation in all stages of atherosclerosis has been actively investigated, with an emphasis on the discovery of novel and innovative drugs for treatment and prevention. The anti-inflammatory and immunomodulatory capacity of cannabinoids are well established, and these agents have a broad therapeutic potential in various inflammatory diseases, including cardiovascular diseases. The aim of this study was to investigate the effect of WIN55212-2, a synthetic cannabinoid, on atherosclerosis using the apolipoprotein E-knockout (ApoE(-/-)) mouse on a cholate-containing high-fat diet. Our results showed that WIN55212-2 reduced the size of atherosclerotic lesions in the aorta root, and did not affect serum lipid levels significantly. Furthermore, alleviation of atherosclerosis by WIN55212-2 was associated with a smaller content of macrophages in plaque lesion as well as decreasing pro-inflammatory gene expression and NF-κB activation in aortic tissues. Oxidized LDL (ox-LDL) dramatically induced NF-κB activation, and enhanced pro-inflammatory mRNA and protein expression in peritoneal macrophages isolated from ApoE(-/-) mice. It is noteworthy that all of the above-mentioned effects of ox-LDL were attenuated by WIN55212-2. Moreover, WIN55212-2 also attenuated the inflammatory response that LPS induced. AM630, a cannabinoid receptor 2 (CB₂) special antagonist completely abolished the protective effects of WIN55212-2 both in vivo and in vitro. Our data provide strong evidence that WIN55212-2 can potentially inhibit atherosclerosis in ApoE(-/-) mice. Importantly, all the beneficial effects of WIN55212-2 in our model were closely associated with the suppression of pro-inflammatory responses and were mediated by the CB₂ receptor. |
| | |
Authors:
|
Yan Zhao; Yan Liu; Weiping Zhang; Jiahong Xue; Yue Z Wu; Wei Xu; Xiao Liang; Tao Chen; Chiharu Kishimoto; Zuyi Yuan |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-21 |
Journal Detail:
|
Title: European journal of pharmacology Volume: 649 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-01 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 285-92 Citation Subset: IM |
Copyright Information:
|
Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
|
Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Effects of cyclic phosphatidic acid on delayed neuronal death following transient ischemia in rat hi...
Next Document: Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine.