Cited by 107Cholesterol and Lipid MetabolismCaveolin-1 and cellular processesNitric Oxide and Endothelin Effects

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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Terasaka, Naoki, Westerterp, Marit, Koetsveld, Joris, Fernández-Hernando, Carlos, Yvan-Charvet, Laurent, Wang, Nan, Sessa, William C., Tall, Alan R.·2010·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract

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. Conclusion— The promotion of cholesterol efflux via ABCG1 results in a reduced inhibitory interaction of eNOS with Cav-1.

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Authors
Terasaka, N., Westerterp, M., Koetsveld, J., Fernández-Hernando, C., Yvan-Charvet, L., Wang, N., Sessa, W. C., & Tall, A. R.
Affiliations
  • Yale University (US)
  • From the Division of Molecular Medicine (N.T., M.W., J.K., L.Y.-C., N.W., and A.R.T.), the Department of Medicine, Columbia University, New York, NY; and the Department of Pharmacology and Vascular Biology and the Therapeutics Program (C.F.-H. and W.C.S.), Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Conn.
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2010-11
Volume
30
Issue
11
Pages
2219-2225
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W2105971827
Cited by
107
References
46
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 14 · 2013: 19 · 2012: 9
FWCI
12.81
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • PubMed Central (acceptedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL061371, R37HL061371)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
ABCG1, high-density lipoprotein, caveolin-1, endothelial nitric oxide synthase, cholesterol efflux, endothelial dysfunction, nitric oxide production, endothelial cells, HDL cholesterol
MeSH terms
ATP Binding Cassette Transporter, Subfamily G, Member 1, Animals, Humans, Cholesterol, HDL, Nitric Oxide, ATP-Binding Cassette Transporters, Endothelial Cells, Caveolin 1, Mice, Nitric Oxide Synthase Type III

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