Document Detail


Cilostazol enhances macrophage reverse cholesterol transport in vitro and in vivo.
MedLine Citation:
PMID:  20723893     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Recent failure of an HDL-cholesterol raising strategy using a cholesteryl ester transfer protein inhibitor highlights the importance of the anti-atherogenic function rather than plasma concentration of HDL. Cilostazol, a selective inhibitor of phosphodiesterase 3, has been widely used in patients with atherosclerotic diseases and is known to increase HDL-cholesterol. However, it remains unclear whether cilostazol enhances anti-atherogenic properties by promoting reverse cholesterol transport (RCT), a major anti-atherogenic function of HDL.
METHODS AND RESULTS: We observed that treatment of THP-1 macrophages, human monocyte-derived macrophages, and RAW264.7 cells with cilostazol increased ABCA1 and ABCG1 expression in a concentration-dependent manner, translating into enhanced apoA-I- and HDL-mediated cholesterol efflux from the macrophages. However, other cyclic AMP (cAMP)-elevating agents did not increase ABCA1 gene expression in THP-1 macrophages. Cilostazol did not change intracellular cAMP levels in THP-1 macrophages and RAW264.7 cells, and a protein kinase A (PKA) inhibitor did not affect cilostazol-induced ABCA1 and ABCG1 expression. To further investigate RCT in vivo, (3)H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were intraperitoneally injected into mice and the appearance of the (3)H-tracer was monitored in plasma, liver, and feces. Supporting the in vitro data, cilostazol was found to significantly increase (3)H-tracer levels in both plasma and feces.
CONCLUSIONS: These findings indicate that cilostazol might provide anti-atherosclerotic effects by promoting RCT through increased ABCA1/G1 expression in macrophages.
Authors:
Kazuhiro Nakaya; Makoto Ayaori; Harumi Uto-Kondo; Tetsuya Hisada; Masatsune Ogura; Emi Yakushiji; Shunichi Takiguchi; Yoshio Terao; Hideki Ozasa; Makoto Sasaki; Tomohiro Komatsu; Fumitaka Ohsuzu; Katsunori Ikewaki
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Publication Detail:
Type:  In Vitro; Journal Article     Date:  2010-07-27
Journal Detail:
Title:  Atherosclerosis     Volume:  213     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-25     Completed Date:  2011-03-07     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  135-41     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Affiliation:
Division of Anti-aging, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
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MeSH Terms
Descriptor/Qualifier:
Bile / metabolism
Biological Transport
Cholesterol / metabolism*
Cholesterol, HDL / metabolism
Cyclic AMP / metabolism
Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism
Humans
Liver / metabolism
Macrophages / metabolism*
Models, Biological
Phosphodiesterase 3 Inhibitors / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Tetrazoles / pharmacology*
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Phosphodiesterase 3 Inhibitors; 0/Tetrazoles; 57-88-5/Cholesterol; 60-92-4/Cyclic AMP; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 3; N7Z035406B/cilostazol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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