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首页> 外文期刊>Biological chemistry >Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V.
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Synthesis of recombinant high density lipoprotein with apolipoprotein A-I and apolipoprotein A-V.

机译:载脂蛋白A-I和载脂蛋白A-V的重组高密度脂蛋白的合成。

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摘要

It has been shown that apolipoprotein A-V (apoA-V) over-expression significantly lowers plasma triglyceride levels and decreases atherosclerotic lesion development. To assess the feasibility of recombinant high density lipoprotein (rHDL) reconstituted with apoA-V and apolipoprotein A-I (apoA-I) as a therapeutic agent for hyperlipidemic disorder and atherosclerosis, a series of rHDL were synthesized in vitro with various mass ratios of recombinant apoA-I and apoA-V. It is interesting to find that apoA-V of rHDL had no effect on lipoprotein lipase (LPL) activation in vitro and very low density lipoprotein (VLDL) clearance in HepG2 cells and in vivo. By contrast, LPL activation and VLDL clearance were inhibited by the addition of apoA-V to rHDL. Furthermore, the apoA-V of rHDL could not redistribute from rHDL to VLDL after incubation at 37 degrees C for 30 min. These findings suggest that an increase of apoA-V in rHDL could not play a role in VLDL clearance in vitro and in vivo, which could, at least in part, attribute to the lost redistribution of apoA-V from rHDL to VLDL and LPL binding ability of apoA-V in rHDL. The therapeutic application of rHDL reconstituted with apoA-V and apoA-I might need the construction of rHDL from which apoA-V could freely redistribute to VLDL.
机译:已经表明,载脂蛋白A-V(apoA-V)的过表达显着降低血浆甘油三酯水平并减少动脉粥样硬化病变的发展。为了评估用apoA-V和载脂蛋白AI(apoA-I)重构的重组高密度脂蛋白(rHDL)作为高脂血症和动脉粥样硬化治疗剂的可行性,在体外合成了一系列质量比不同的重组apoA的rHDL -I和apoA-V。有趣的是,rHDL的apoA-V在体外对脂蛋白脂酶(LPL)的活化没有影响,在HepG2细胞和体内对密度很低的脂蛋白(VLDL)的清除率没有影响。相比之下,通过在rHDL中添加apoA-V可以抑制LPL激活和VLDL清除。此外,在37°C孵育30分钟后,rHDL的apoA-V无法从rHDL重新分布到VLDL。这些发现表明,在体外和体内,rHDL中apoA-V的增加不能在VLDL清除中起作用,这至少可以部分归因于apoA-V从rHDL到VLDL和LPL结合的重新分布丢失。 rHDL中apoA-V的能力。用apoA-V和apoA-I重建的rHDL的治疗应用可能需要构建rHDL,apoA-V可以从中自由重新分布到VLDL。

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