PMID- 20798376 OWN - NLM STAT- MEDLINE DCOM- 20101220 LR - 20211020 IS - 1524-4636 (Electronic) IS - 1079-5642 (Print) IS - 1079-5642 (Linking) VI - 30 IP - 11 DP - 2010 Nov TI - 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. PG - 2219-25 LID - 10.1161/ATVBAHA.110.213215 [doi] AB - 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. FAU - Terasaka, Naoki AU - Terasaka N AD - Division of Molecular Medicine, Department of Medicine, Columbia University, 630 W 168 St, New York, NY 10032, USA. FAU - Westerterp, Marit AU - Westerterp M FAU - Koetsveld, Joris AU - Koetsveld J FAU - Fernandez-Hernando, Carlos AU - Fernandez-Hernando C FAU - Yvan-Charvet, Laurent AU - Yvan-Charvet L FAU - Wang, Nan AU - Wang N FAU - Sessa, William C AU - Sessa WC FAU - Tall, Alan R AU - Tall AR LA - eng GR - R01 HL061371/HL/NHLBI NIH HHS/United States GR - R37 HL061371/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100826 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (ABCG1 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Caveolin 1) RN - 0 (Cholesterol, HDL) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (NOS3 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) SB - IM MH - ATP Binding Cassette Transporter, Subfamily G, Member 1 MH - ATP-Binding Cassette Transporters/*metabolism MH - Animals MH - Caveolin 1/*metabolism MH - Cholesterol, HDL/*metabolism MH - Endothelial Cells MH - Humans MH - Mice MH - Nitric Oxide/*biosynthesis MH - Nitric Oxide Synthase Type III/*metabolism PMC - PMC4790108 MID - NIHMS759718 EDAT- 2010/08/28 06:00 MHDA- 2010/12/21 06:00 PMCR- 2016/03/14 CRDT- 2010/08/28 06:00 PHST- 2010/08/28 06:00 [entrez] PHST- 2010/08/28 06:00 [pubmed] PHST- 2010/12/21 06:00 [medline] PHST- 2016/03/14 00:00 [pmc-release] AID - ATVBAHA.110.213215 [pii] AID - 10.1161/ATVBAHA.110.213215 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2219-25. doi: 10.1161/ATVBAHA.110.213215. Epub 2010 Aug 26.