| Effect of Sulfonylurea Agents on Reverse Cholesterol Transport in Vitro and Vivo. | |
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MedLine Citation:
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PMID: 21636950 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aim: Reverse cholesterol transport (RCT) is a critical mechanism for the anti-atherogenic property of HDL. The inhibitory effect of the sulfonylurea agent (SUA) glibenclamide on ATP binding-cassette transporter (ABC) A1 may decrease HDL function but it remains unclear whether it attenuates RCT in vivo. We therefore investigated how the SUAs glibenclamide and glimepiride affected the functionality of ABCA1/ABCG1 and scavenger receptor class B type I (SR-BI) expression in macrophages in vitro and overall RCT in vivo.Methods: RAW264.7, HEK293 and BHK-21 cells were used for in vitro studies. To investigate RCT in vivo, 3H-cholesterol-labeled and acetyl LDL-loaded RAW264.7 cells were injected into mice.Results: High dose (500µM) of glibenclamide inhibited ABCA1 function and apolipoprotein A-I (apoA-I)-mediated cholesterol efflux, and attenuated ABCA1 expression. Although glimepiride maintained apoA-I-mediated cholesterol efflux from RAW264.7 cells, like glibenclamide, it inhibited ABCA1-mediated cholesterol efflux from transfected HEK293 cells. Similarly, the SUAs inhibited SR-BI-mediated cholesterol efflux from transfected BHK-21 cells. High doses of SUAs increased ABCG1 expression in RAW264.7 cells, promoting HDL-mediated cholesterol efflux in an ABCG1-independent manner. Low doses (0.1-100 µM) of SUAs did not affect cholesterol efflux from macrophages despite dose-dependent increases in ABCA1/G1 expression. Furthermore, they did not change RCT or plasma lipid levels in mice.Conclusion: High doses of SUAs inhibited the functionality of ABCA1/SR-BI, but not ABCG1. At lower doses, they had no unfavorable effects on cholesterol efflux or overall RCT in vivo. These results indicate that SUAs do not have adverse effects on atherosclerosis contrary to previous findings for glibenclamide. |
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Authors:
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Yoshio Terao; Makoto Ayaori; Masatsune Ogura; Emi Yakushiji; Harumi Uto-Kondo; Tetsuya Hisada; Hideki Ozasa; Shunichi Takiguchi; Kazuhiro Nakaya; Makoto Sasaki; Tomohiro Komatsu; Maki Iizuka; Shunpei Horii; Katsunori Ikewaki |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-3 |
Journal Detail:
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Title: Journal of atherosclerosis and thrombosis Volume: - ISSN: 1880-3873 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-3 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9506298 Medline TA: J Atheroscler Thromb Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Anti-aging, Department of Internal Medicine, National Defense Medical College. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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