Division of Molecular Medicine, Department of Medicine, Columbia University, 630 W 168 St, New York, NY 10032, USA.
Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2219-25. doi: 10.1161/ATVBAHA.110.213215. Epub 2010 Aug 26.
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).
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.
The promotion of cholesterol efflux via ABCG1 results in a reduced inhibitory interaction of eNOS with Cav-1.
研究胆固醇通过 ATP 结合盒转运蛋白 G1（ABCG1）向高密度脂蛋白（HDL）外排是否调节小窝蛋白（Cav）1 和内皮型一氧化氮合酶（eNOS）之间的相互作用。
ABCG1 促进内皮细胞（EC）中的胆固醇和 7-氧代胆固醇向 HDL 的外排。先前的研究表明，ABCG1 通过促进 7-氧代胆固醇向 HDL 的外排来保护内皮细胞免受饮食胆固醇诱导的功能障碍。已知 EC 中胆固醇负荷的增加会导致 Cav-1 与 eNOS 之间的抑制性相互作用，并损害 NO 的释放。在人主动脉 EC 中，游离胆固醇负荷促进了 Cav-1 与 eNOS 的相互作用，降低了 eNOS 活性。这些胆固醇负荷的影响可以通过 ABCG1 依赖的方式被 HDL 逆转。HDL 还可以逆转胆固醇负荷对小鼠肺 ECs 中 eNOS 的抑制作用，但这种 HDL 的作用在 Cav-1 缺陷型小鼠肺 ECs 中被消除。在高胆固醇饮食喂养的 Abcg1（-/-）小鼠的主动脉匀浆中也检测到 Cav-1 与 eNOS 的相互作用增加，同时 eNOS 活性降低和内皮功能受损。
通过 ABCG1 促进胆固醇外排会导致 eNOS 与 Cav-1 的抑制性相互作用减少。
