The 5A apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitro.
The 5A apolipoprotein A-I mimetic peptide displays antiinflammatory and antioxidant properties in vivo and in vitro.
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DOI：
10.1161/atvbaha.109.200196
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发表时间：
2010-02
期刊：
影响因子：
--
通讯作者：
Lambert G
中科院分区：
文献类型：
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作者：
Tabet F;Remaley AT;Segaliny AI;Millet J;Yan L;Nakhla S;Barter PJ;Rye KA;Lambert G
载脂蛋白(Apo)A-I模拟肽5A对ABCA1转运体介导的胆固醇外流具有高度的特异性。我们研究了5A肽是否具有apoA-I的其他有益特征，如抗炎和抗氧化。新西兰大白兔接受apoA-I，即含有apoA-I的重组高密度脂蛋白((A-I)rHDL)或与磷脂络合物的5A肽(PLPC)的输注，然后在颈动脉周围插入项圈。人冠状动脉内皮细胞(HCAECs)与(A-I)rHDLc或5A/PLPC孵育后，再进行TNFa刺激。载脂蛋白A-I、(A-I)重组高密度脂蛋白和5A/PLPC可减少细胞黏附分子VCAM-1和ICAM-1的内皮细胞表达、O2−的产生和NADPH氧化酶催化亚基的表达，以及(Iii)循环中性粒细胞向颈动脉内膜中层的渗透。在HCAECs中，5A/plpC和(A-I)rHDL都能抑制TNFa诱导的细胞间黏附分子-1和血管细胞间黏附分子-1的表达，并抑制NF-κB信号转导通路和O2-−的产生。在ABCA1基因敲除的HCAEC中，5A/PLPC复合体的作用不再明显。与apoA-I一样，5A肽可抑制兔颈总动脉和HCAEC的急性炎症和氧化应激。在体外，5A肽通过与ABCA1的相互作用发挥这些有益的作用。
The apolipoprotein (apo) A-I mimetic peptide 5A is highly specific for ABCA1-transporter mediated cholesterol efflux. We investigated whether the 5A peptide shares other beneficial features of apoA-I, such as protection against inflammation and oxidation. New-Zealand White rabbits received an infusion of apoA-I, reconstituted HDL containing apoA-I ((A-I)rHDL) or the 5A peptide complexed with phospholipids (PLPC), prior to inserting a collar around the carotid artery. Human coronary artery endothelial cells (HCAECs) were incubated with (A-I)rHDL or 5A/PLPC prior to TNFa stimulation. ApoA-I, (A-I)rHDL and 5A/PLPC reduced the collar mediated increase in (i) endothelial expression of cell adhesion molecules VCAM-1 and ICAM-1, (ii) O2− production as well as the expression of the Nox4 catalytic subunits of the NADPH oxidase, and (iii) infiltration of circulating neutrophils into the carotid intima-media. In HCAECs, both 5A/PLPC and (A-I)rHDL inhibited TNFa induced ICAM-1 and VCAM-1 expression as well as the NF-κB signalling cascade and O2− production. The effects of the 5A/PLPC complex were no longer apparent in HCAECs knocked down for ABCA1. Like apoA-I, the 5A peptide inhibits acute inflammation and oxidative stress in rabbit carotids and HCAECs. In vitro, the 5A peptide exerts these beneficial effects through interaction with ABCA1.