Endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes its subendothelial retention in vascular wall.
Endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes its subendothelial retention in vascular wall.
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DOI：
10.1155/2014/823071
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发表时间：
2014
影响因子：
--
通讯作者：
Jin S
中科院分区：
文献类型：
--
作者：
Li W;Yang X;Xing S;Bian F;Yao W;Bai X;Zheng T;Wu G;Jin S
氧化低密度脂蛋白（Oxidized low density of lipoprotein，oxLDL）是动脉粥样硬化病变中的主要脂质，血浆oxLDL升高被认为是动脉粥样硬化的危险因素。血浆oxLDL是否能通过内皮细胞转运并引发动脉粥样硬化的改变尚不清楚。在体外细胞转胞吞模型中，本研究发现oxLDL可以跨血管内皮细胞运输，并进一步发现神经酰胺代谢酶抑制剂对内源性神经酰胺产生的调节显著改变了oxLDL跨内皮细胞的转胞吞。结果发现，酸性鞘磷脂酶抑制剂地昔帕明（DES）和神经酰胺合成抑制剂myriocin（MYR），都减少内源性神经酰胺的产生，显着抑制oxLDL的转胞吞作用。神经酰胺酶抑制剂N-油酰乙醇胺（NOE）和鞘磷脂合成酶抑制剂O-三环[5.2.1.02，6]癸-9-基二硫代碳酸钾盐（D 609）均增加内源性神经酰胺的产生，显著上调oxLDL的转胞吞作用。在体内，将荧光标记的oxLDL注射到小鼠体内也倾向于这些氧化脂质的内皮下滞留。本研究中提供的观察结果表明，内源性神经酰胺有助于oxLDL跨内皮细胞的转胞吞，并促进动脉粥样硬化的起始步骤-脂质在血管壁中的内皮下滞留。
Oxidized low density of lipoprotein (oxLDL) is the major lipid found in atherosclerotic lesion and elevated plasma oxLDL is recognized to be a risk factor of atherosclerosis. Whether plasma oxLDL could be transported across endothelial cells and initiate atherosclerotic changes remains unknown. In an established in vitro cellular transcytosis model, the present study found that oxLDL could traffic across vascular endothelial cells and further that the regulation of endogenous ceramide production by ceramide metabolizing enzyme inhibitors significantly altered the transcytosis of oxLDL across endothelial cells. It was found that acid sphingomyelinase inhibitor, desipramine (DES), and de novo ceramide synthesis inhibitor, myriocin (MYR), both decreasing the endogenous ceramide production, significantly inhibited the transcytosis of oxLDL. Ceramidase inhibitor, N-oleoylethanolamine (NOE), and sphingomyelin synthase inhibitor, O-Tricyclo[5.2.1.02,6]dec-9-yl dithiocarbonate potassium salt (D609), both increasing the endogenous ceramide production, significantly upregulated the transcytosis of oxLDL. In vivo, injection of fluorescence labeled oxLDL into mice body also predisposed to the subendothelial retention of these oxidized lipids. The observations provided in the present study demonstrate that endogenous ceramide contributes to the transcytosis of oxLDL across endothelial cells and promotes the initiating step of atherosclerosis—the subendothelial retention of lipids in vascular wall.
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DOI：
10.1042/cs20090452
发表时间：
2010-03-30
期刊：
Clinical science (London, England : 1979)
影响因子：
--
作者：
Glaros EN;Kim WS;Garner B
通讯作者：
Garner B
影响因子：
3.4
作者：
Cankova, Zdravka;Huang, Jiahn-Dar;Kruth, Howard S.;Johnson, Mark
通讯作者：
Johnson, Mark
影响因子：
37.8
作者：
Ehara, S;Ueda, M;Becker, AE
通讯作者：
Becker, AE
DOI：
10.1161/01.atv.20.12.2614
发表时间：
2000-12-01
影响因子：
8.7
作者：
Jiang, XC;Paultre, F;Tall, AR
通讯作者：
Tall, AR
影响因子：
6.6
作者：
Jin, Si;Yi, Fan;Li, Pin-Lan
通讯作者：
Li, Pin-Lan