Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, USA,
Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, Tennessee, USA.
J Vasc Res. 2022;59(5):275-287. doi: 10.1159/000525259. Epub 2022 Jun 27.
Caveola-located scavenger receptor type B class I (SR-BI) and activin receptor-like kinase-1 (ALK1) are involved in transendothelial transport of apolipoprotein B-carrying lipoproteins (apoB-LPs). Transport of apoB-LPs though mouse aortic endothelial cells (MAECs) is associated with apoE-carrying high-density lipoprotein (HDL)-like particle formation and apoAI induces raft-located proteins to shift to non-raft membranes by upregulation of ATP-binding cassette transporter A1 (ABCA1). To investigate apoAI's effect on transendothelial transport of apoB-LPs, MAECs and human coronary artery endothelial cells (HCAECs) were treated with apoB-LPs ± apoAI. Our data demonstrated that apoAI neither altered SR-BI and ALK1 expression nor affected apoB-LP binding to MAECs. ApoAI inhibited MAEC uptake, transcellular transport, and intracellular accumulation of apoB-LPs and accelerated their resecretion in MAECs. ApoAI enhanced transendothelial apoB-LP transport-associated HDL-like particle formation, upregulated ABCA1 expression, shifted SR-BI and ALK1 to the non-raft membrane in MAECs, inhibited transcellular transport of apoB-LPs, and enhanced associated HDL-like particle formation in HCAECs. ABCA1 knockdown attenuated apoAI-induced membrane SR-BI and ALK1 relocation and diminished apoAI's effect on transendothelial apoB-LP transport and HDL-like particle formation in MAECs. This suggests that upregulation of ABCA1 expression is a mechanism, whereby apoAI provokes caveola-located receptor relocation, inhibits transendothelial apoB-LP transport, and promotes associated HDL-like particle formation.
窖蛋白定位的清道夫受体 B 类 I 型（SR-BI）和激活素受体样激酶-1（ALK1）参与载脂蛋白 B 脂蛋白（apoB-LP）的跨内皮转运。通过小鼠主动脉内皮细胞（MAECs）的 apoB-LP 转运与载 apoE 的高密度脂蛋白（HDL）样颗粒形成有关，并且 apoAI 通过上调三磷酸腺苷结合盒转运体 A1（ABCA1）诱导筏定位蛋白向非筏膜转移。为了研究 apoAI 对 apoB-LP 跨内皮转运的影响，用 apoB-LP±apoAI 处理 MAECs 和人冠状动脉内皮细胞（HCAECs）。我们的数据表明，apoAI 既不改变 SR-BI 和 ALK1 的表达，也不影响 apoB-LP 与 MAECs 的结合。apoAI 抑制 MAEC 摄取、跨细胞转运和细胞内 apoB-LP 积累，并加速其在 MAECs 中的再分泌。apoAI 增强 apoB-LP 转运相关 HDL 样颗粒形成，上调 ABCA1 表达，将 SR-BI 和 ALK1 转移至 MAECs 的非筏膜，抑制 apoB-LP 的跨细胞转运，并增强 HCAECs 中相关的 HDL 样颗粒形成。ABCA1 敲低减弱了 apoAI 诱导的膜 SR-BI 和 ALK1 重定位，并减弱了 apoAI 对 MAECs 中 apoB-LP 跨内皮转运和 HDL 样颗粒形成的作用。这表明 ABCA1 表达的上调是一种机制，apoAI 引发窖蛋白定位受体重定位，抑制 apoB-LP 的跨内皮转运，并促进相关的 HDL 样颗粒形成。
