| Cilostazol enhances macrophage reverse cholesterol transport in vitro and in vivo. | |
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MedLine Citation:
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PMID: 20723893 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article Date: 2010-07-27 |
Journal Detail:
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Title: Atherosclerosis Volume: 213 ISSN: 1879-1484 ISO Abbreviation: Atherosclerosis Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 135-41 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Division of Anti-aging, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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