Accumulation of unesterified cholesterol-rich lipid vesicles in the subendothelial space contributes to atherogenesis. Transport of cholesterol from the subendothelial intima back to the circulating blood inhibits atherosclerosis development; however, the mechanism for this process has not been fully defined. Using cultured mouse aortic endothelial cells (MAECs), we observed that unesterified cholesterol can be transported across the endothelial cell monolayer from the basolateral to the apical compartment. Administration of high-density lipoprotein (HDL) or apolipoprotein AI (apoAI) to the apical compartment enhanced transendothelial cholesterol transport in a concentration-dependent manner. Knockdown of ATP-binding cassette transporter G1 (ABCG1) or scavenger receptor class B type I (SR-B1), or inhibition of SR-B1 diminished HDL-induced transendothelial cholesterol transport; while knockdown of ABCA1 reduced apoAI-mediated cholesterol transport. HDL enhanced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt in MAECs. However, inhibition of PI3K or Akt did not reduce HDL-induced transendothelial cholesterol transport. These results suggest that HDL enhances transendothelial cholesterol transport by activation of a mechanism involving ABCA1, ABCG1 and SR-B1 but not involving PI3K and Akt.

中文翻译：

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小鼠主动脉内皮细胞中高密度脂蛋白介导的跨细胞胆固醇转运。

未酯化的富含胆固醇的脂质囊泡在内皮下空间的积累有助于动脉粥样硬化的形成。胆固醇从内皮下内膜向循环血液的运输抑制了动脉粥样硬化的发展。但是，此过程的机制尚未完全定义。使用培养的小鼠主动脉内皮细胞（MAECs），我们观察到未酯化的胆固醇可以通过内皮细胞单层从基底外侧转运到根尖区。向心室施用高密度脂蛋白（HDL）或载脂蛋白AI（apoAI）以浓度依赖的方式增强了跨内皮胆固醇的转运。击倒ATP结合盒转运蛋白G1（ABCG1）或I类清道夫受体B（SR-B1），或抑制SR-B1减少了HDL诱导的跨内皮胆固醇运输；而敲低ABCA1可减少apoAI介导的胆固醇转运。HDL增强了MAEC中磷脂酰肌醇3-激酶（PI3K）和Akt的磷酸化。但是，抑制PI3K或Akt不会降低HDL诱导的跨内皮胆固醇的转运。这些结果表明，HDL通过激活涉及ABCA1，ABCG1和SR-B1但不涉及PI3K和Akt的机制来增强跨内皮胆固醇的转运。