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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

Terasaka, N., Westerterp, M., Koetsveld, J., Fernández-Hernando, C., Yvan-Charvet, L., Wang, N., Sessa, W. C. & Tall, A. R., Nov-2010, In : Arteriosclerosis, thrombosis, and vascular biology. 30, 11, p. 2219-2225 7 p.

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  • 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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DOI

  • Naoki Terasaka
  • Marit Westerterp
  • Joris Koetsveld
  • Carlos Fernández-Hernando
  • Laurent Yvan-Charvet
  • Nan Wang
  • William C Sessa
  • Alan R Tall

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.

Original languageEnglish
Pages (from-to)2219-2225
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number11
Publication statusPublished - Nov-2010

    Keywords

  • ATP Binding Cassette Transporter, Subfamily G, Member 1, ATP-Binding Cassette Transporters/metabolism, Animals, Caveolin 1/metabolism, Cholesterol, HDL/metabolism, Endothelial Cells, Humans, Mice, Nitric Oxide/biosynthesis, Nitric Oxide Synthase Type III/metabolism

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