| ATP-binding cassette transporter G1 and high-density lipoprotein promote endothelial NO synthesis through a decrease in the interaction of caveolin-1 and endothelial NO synthase. | |
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MedLine Citation:
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PMID: 20798376 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To investigate whether cholesterol efflux to high-density lipoprotein (HDL) via ATP-binding cassette transporter G1 (ABCG1) modulates the interaction of caveolin (Cav) 1 and endothelial NO synthase (eNOS). METHODS AND RESULTS: ABCG1 promotes cholesterol and 7-oxysterol efflux from endothelial cells (ECs) to HDL. It was previously reported that ABCG1 protects against dietary cholesterol-induced endothelial dysfunction by promoting the efflux of 7-oxysterols to HDL. Increased cholesterol loading in ECs is known to cause an inhibitory interaction between Cav-1 and eNOS and impaired NO release. In human aortic ECs, free cholesterol loading promoted the interaction of Cav-1 with eNOS, reducing eNOS activity. These effects of cholesterol loading were reversed by HDL in an ABCG1-dependent manner. HDL also reversed the inhibition of eNOS by cholesterol loading in murine lung ECs, but this effect of HDL was abolished in Cav-1-deficient murine lung ECs. Increased interaction of Cav-1 with eNOS was also detected in aortic homogenates of high-cholesterol diet-fed Abcg1(-/-) mice, paralleling a decrease in eNOS activity and impaired endothelial function. CONCLUSIONS: The promotion of cholesterol efflux via ABCG1 results in a reduced inhibitory interaction of eNOS with Cav-1. |
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Authors:
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Naoki Terasaka; Marit Westerterp; Joris Koetsveld; Carlos Fernández-Hernando; Laurent Yvan-Charvet; Nan Wang; William C Sessa; Alan R Tall |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-26 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-12-20 Revised Date: 2011-01-14 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2219-25 Citation Subset: IM |
Affiliation:
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Division of Molecular Medicine, Department of Medicine, Columbia University, 630 W 168 St, New York, NY 10032, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ATP-Binding Cassette Transporters
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metabolism* Animals Caveolin 1 / metabolism* Cholesterol, HDL / metabolism* Endothelial Cells Humans Mice Nitric Oxide / biosynthesis* Nitric Oxide Synthase Type III / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R37 HL061371-13/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/ABCG1 protein, human; 0/ATP-Binding Cassette Transporters; 0/Caveolin 1; 0/Cholesterol, HDL; 10102-43-9/Nitric Oxide; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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