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血管生成素样蛋白4:一种新型酶联免疫吸附测定法的研发、分析特性及临床检测

Angiopoietin-like protein 4: development, analytical characterization, and clinical testing of a new ELISA.

作者信息

Stejskal D, Karpísek M, Reutová H, Humenanská V, Petzel M, Kusnierová P, Vareka I, Vareková R, Stejskal P

机构信息

Department of Laboratory Medicine, Sternberk Hospital, Jivavská 20, 785 16 Sternberk, Czech Republic.

出版信息

Gen Physiol Biophys. 2008 Mar;27(1):59-63.

PMID:18436985
Abstract

The aim of our work was to develop an assay for the determination of angiopoietin-like protein 4 (Angplt4) in human blood, and to investigate its levels in healthy volunteers and donors suffer from metabolic syndrome. We developed and evaluated the sandwich ELISA method for the quantitative determination of human Angplt4 in serum samples. We conducted also the pilot study on individuals with metabolic syndrome or familiar hypercholesterolemia and healthy probands and measured blood pressure, waist circumference, Angplt4 serum levels, serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, insulin, glucose, A-FABP and calculate BMI and QUICKI insulin sensitivity index. In the study on 30 healthy volunteers we demonstrated that sex or age is not the determinant for Angplt4 serum values. Furthermore, we tested 115 individuals with metabolic syndrome and found that probands with metabolic syndrome did not differ in Angplt4 values than healthy individuals from the first study (medians 8.7 vs. 8.1 ng/ml, p = 0.6). Individuals with metabolic syndrome did not differ in sex or age from healthy. Angplt4 values correlated with the HDL-cholesterol (r = -0.25; p < 0.01), FGF-21 (r = 0.23, p < 0.01), glucose (r = 0.17; p = 0.03), uric acid (r = 0.17; p = 0.49), lipocalin-2 (r = 0.23, p < 0.01), triacylglycerols (r = 0.25; p < 0.01) and number or characters of metabolic syndrome (r = 0.21; p < 0.01). No significant correlation was found between serum Angplt4 and BMI, WC or QUICKI. However, we performed stepwise regression and we found that Angplt4 was not an independent marker for metabolic syndrome. The patients from the metabolic syndrome group suffering diabetes mellitus (n = 83) did not differ in serum Angplt4 from the group of healthy patients, too. The pilot study supports the hypothesis about the role of Angplt4 as a new class of lipid metabolism modulator. Their values could be a new key predictors of metabolic syndrome. Further research is necessary to confirm our findings in individuals with dyslipidemia, obesity, coronary artery diseases and different medication in order to assess Angplt4 value as a risk predictor of accelerated atherosclerosis.

摘要

我们工作的目的是开发一种用于测定人血液中血管生成素样蛋白4(Angplt4)的检测方法,并研究其在健康志愿者和患有代谢综合征的献血者中的水平。我们开发并评估了用于定量测定血清样本中人类Angplt4的夹心ELISA方法。我们还对患有代谢综合征或家族性高胆固醇血症的个体以及健康对照者进行了初步研究,测量了血压、腰围、Angplt4血清水平、血清胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、胰岛素、葡萄糖、脂肪型脂肪酸结合蛋白(A-FABP),并计算了体重指数(BMI)和定量胰岛素敏感性检查指数(QUICKI)。在对30名健康志愿者的研究中,我们证明性别或年龄不是Angplt4血清值的决定因素。此外,我们对115名患有代谢综合征的个体进行了测试,发现患有代谢综合征的对照者与第一项研究中的健康个体在Angplt4值上没有差异(中位数分别为8.7与8.1 ng/ml,p = 0.6)。患有代谢综合征的个体在性别或年龄上与健康个体没有差异。Angplt4值与高密度脂蛋白胆固醇(r = -0.25;p < 0.01)、成纤维细胞生长因子21(FGF-21,r = 0.23,p < 0.01)、葡萄糖(r = 0.17;p = 0.03)、尿酸(r = 0.17;p = 0.49)、lipocalin-2(r = 0.23,p < 0.01)、甘油三酯(r = 0.25;p < 0.01)以及代谢综合征的数量或特征(r = 0.21;p < 0.01)相关。血清Angplt4与BMI、腰围或QUICKI之间未发现显著相关性。然而,我们进行了逐步回归分析,发现Angplt4不是代谢综合征的独立标志物。患有糖尿病的代谢综合征组患者(n = 83)与健康患者组在血清Angplt4方面也没有差异。初步研究支持了关于Angplt4作为一类新的脂质代谢调节剂作用的假设。其值可能是代谢综合征的新关键预测指标。有必要进行进一步研究,以在患有血脂异常、肥胖、冠状动脉疾病以及使用不同药物的个体中证实我们的发现,以便评估Angplt4值作为动脉粥样硬化加速风险预测指标的价值。

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引用本文的文献

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Effect of mountain ultra-marathon running on plasma angiopoietin-like protein 4 and lipid profile in healthy trained men.健康训练男性进行山地超级马拉松跑对血浆血管生成素样蛋白 4 和血脂谱的影响。
Eur J Appl Physiol. 2020 Jan;120(1):117-125. doi: 10.1007/s00421-019-04256-w. Epub 2019 Nov 9.
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ANGPTL4 in Metabolic and Cardiovascular Disease.
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Trends Mol Med. 2019 Aug;25(8):723-734. doi: 10.1016/j.molmed.2019.05.010. Epub 2019 Jun 21.
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Association of a genetic variant in the angiopoietin-like protein 4 gene with metabolic syndrome.血管生成素样蛋白4基因中的一个基因变异与代谢综合征的关联。
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ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels and predicts cardiovascular disease risk in Type 2 diabetic Tunisian population.血管生成素样蛋白4(ANGPTL4)的E40K和T266M变体与较低的空腹甘油三酯水平相关,并可预测突尼斯2型糖尿病患者的心血管疾病风险。
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