The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells.

The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells.
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DOI:
10.1371/journal.pone.0123971
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Huang CY
Huang CY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lin FY;Tsao NW;Shih CM;Lin YW;Yeh JS;Chen JW;Nakagami H;Morishita R;Sawamura T;Huang CY

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晚期生长的内皮祖细胞(EPCs)具有抗应激和心血管系统修复功能。氧化型低密度脂蛋白(oxidized LDL,oxLDL)在心血管疾病的发病机制中起重要作用。然而,它在很大程度上是未知的氧化低密度脂蛋白的影响是后期生长的内皮祖细胞。本研究旨在探讨oxLDL对EPC功能和相关血管生成的浓度相关影响,在体外和体内。在这项研究中,早期和晚期生长的EPCs从循环的人单核细胞中产生。oxLDL可能通过凝集素样氧化低密度脂蛋白受体-1(LOX-1)调节EPC血管生成功能。较低浓度(5 μg/mL)的oxLDL可通过激活p38 MAPK和SAPK/JNK相关通路介导的eNOS机制,增强体外和体内EPC管的形成。高浓度oxLDL(10-50 μg/mL)通过激活烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶途径和随后抑制eNOS活性而损害EPC功能,抗氧化剂(二苯碘鎓和夹竹桃素)和gp 91 phox siRNA可逆转该作用。总之,oxLDL在体外和体内对人晚期生长EPC管形成具有浓度依赖性的双相效应。
Late-outgrowth endothelial progenitor cells (EPCs) are stress-resistant and responsible for reparative functions in the cardiovascular system. Oxidized-LDL (oxLDL) plays a critical role in cardiovascular disease pathogenesis. However, it is largely unknown what the impacts of oxLDL are on late-outgrowth EPCs. This study aimed to investigate the concentration-related effects of oxLDL on EPC functions and related angiogenesis, in vitro and in vivo. In this study, early and late-outgrowth EPCs were generated from circulating human mononuclear cells. oxLDL may regulate EPC vasculogenic function via the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Lower concentrations (5 μg/mL) of oxLDL can potentiate EPC tube formation in vitro and in vivo by activating eNOS mechanisms, which are mediated by p38 MAPK- and SAPK/JNK-related pathways. Higher concentrations of oxLDL (10-50 μg/mL) impaired EPC function via the activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathways and consequent inhibition of eNOS activity, which could be reversed by anti-oxidants (diphenylene iodonium and apocynin) and gp91phox siRNA. In conclusion, oxLDL has concentration-dependent biphasic effects on human late-outgrowth EPC tube formation in vitro and in vivo.
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