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 synthaseTerasaka, 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.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||7|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|Publication status||Published - Nov-2010|
- 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