Immuno-Biological Laboratories, Fujioka, Gunma, Japan.
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
J Clin Lipidol. 2018 Jan-Feb;12(1):203-210.e1. doi: 10.1016/j.jacl.2017.10.022. Epub 2017 Nov 1.
Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), a glycosylphosphatidylinositol (GPI)-anchored protein of capillary endothelial cells, transports lipoprotein lipase to the capillary lumen and is essential for the lipolytic processing of triglyceride-rich lipoproteins.
Because some GPI-anchored proteins have been detected in plasma, we tested whether GPIHBP1 is present in human blood and whether GPIHBP1 deficiency or a history of cardiovascular disease affected GPIHBP1 circulating levels.
We developed 2 monoclonal antibodies against GPIHBP1 and used the antibodies to establish a sandwich enzyme-linked immunosorbent assay (ELISA) to measure GPIHBP1 levels in human blood.
The GPIHBP1 ELISA was linear in the 8 to 500 pg/mL range and allowed the quantification of GPIHBP1 in serum and in pre- and post-heparin plasma (including lipemic samples). GPIHBP1 was undetectable in the plasma of subjects with null mutations in GPIHBP1. Serum GPIHBP1 median levels were 849 pg/mL (range: 740-1014) in healthy volunteers (n = 28) and 1087 pg/mL (range: 877-1371) in patients with a history of cardiovascular or metabolic disease (n = 415). There was an extremely small inverse correlation between GPIHBP1 and triglyceride levels (r = 0.109; P < .0275). GPIHBP1 levels tended to be slightly higher in patients who had a major cardiovascular event after revascularization.
We developed an ELISA for quantifying GPIHBP1 in human blood. This assay will be useful to identify patients with GPIHBP1 deficiency and patients with GPIHBP1 autoantibodies. The potential of plasma GPIHBP1 as a biomarker for metabolic or cardiovascular disease is yet questionable but needs additional testing.
糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1(GPIHBP1)是毛细血管内皮细胞的糖基磷脂酰肌醇(GPI)锚定蛋白,它将脂蛋白脂肪酶转运到毛细血管腔中,对于富含甘油三酯的脂蛋白的脂解加工至关重要。
由于已经在血浆中检测到一些 GPI 锚定蛋白,我们检测了 GPIHBP1 是否存在于人类血液中,以及 GPIHBP1 缺乏或心血管疾病史是否会影响 GPIHBP1 的循环水平。
我们针对 GPIHBP1 开发了 2 种单克隆抗体,并使用这些抗体建立了夹心酶联免疫吸附试验(ELISA),以测量人类血液中的 GPIHBP1 水平。
GPIHBP1 ELISA 在 8 至 500pg/mL 范围内呈线性,允许定量检测血清和肝素前及肝素后血浆中的 GPIHBP1(包括脂血样本)。在 GPIHBP1 基因缺失突变的受试者的血浆中无法检测到 GPIHBP1。健康志愿者(n=28)的血清 GPIHBP1 中位数水平为 849pg/mL(范围:740-1014),心血管或代谢疾病史患者(n=415)为 1087pg/mL(范围:877-1371)。GPIHBP1 与甘油三酯水平之间存在极小的负相关(r=0.109;P<0.0275)。在接受血运重建后发生重大心血管事件的患者中,GPIHBP1 水平略有升高的趋势。
我们开发了一种用于定量检测人类血液中 GPIHBP1 的 ELISA。该检测方法将有助于识别 GPIHBP1 缺乏症患者和 GPIHBP1 自身抗体患者。血浆 GPIHBP1 作为代谢或心血管疾病生物标志物的潜力仍有待进一步检测。