Molecular form and concentration of serum α2-macroglobulin in diabetes
Molecular form and concentration of serum α2-macroglobulin in diabetes
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DOI：
10.1038/s41598-019-49144-7
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发表时间：
2019-09-10
影响因子：
4.6
通讯作者：
Shichiri, Masayoshi
中科院分区：
文献类型：
--
作者：
Yoshino, Sonomi;Fujimoto, Kazumi;Shichiri, Masayoshi
α（2）-巨球蛋白是一种高度丰富的血清蛋白，参与动脉粥样硬化和心脏肥大的发展。然而，其循环分子形式和在人类健康/疾病中的确切浓度尚不清楚。人血清的蓝色天然聚丙烯酰胺凝胶电泳用于确认α（2）-巨球蛋白的天然构象。我们建立了一种酶联免疫吸附测定法，适用于定量其循环分子形式，并进行了一项横断面研究，以测量其在248例糖尿病患者和59名健康志愿者的血清水平。α 2-巨球蛋白的主要循环分子形式是四聚体，而在血清α 2-巨球蛋白水平高的患者中可检测到其二聚体。血清α 2-巨球蛋白浓度与糖化血红蛋白或48小时连续血糖监测评估的任何其他血糖变量无关，但与左心室后壁厚度、颈动脉内膜中层厚度、尿白蛋白/肌酐比值（ACR）和臂踝脉搏波速度（baPWV）密切相关。多变量分析显示只有ACR和baPWV是影响血清α 2-巨球蛋白水平的独立变量。因此，增加的ACR和baPWV与更高的α（2）-巨球蛋白血清浓度相关，后者可能有助于蛋白尿增加发生心血管疾病的风险的机制。
alpha(2)-Macroglobulin is a highly abundant serum protein involved in the development of atherosclerosis and cardiac hypertrophy. However, its circulating molecular form and exact concentrations in human health/diseases are not known. Blue native-polyacrylamide gel electrophoresis of human serum was used to confirm the native conformation of alpha(2)-macroglobulin. We created an enzyme-linked immunosorbent assay suitable for quantifying its circulating molecular form and undertook a cross-sectional study to measure its serum levels in 248 patients with diabetes mellitus and 59 healthy volunteers. The predominant circulating molecular form of alpha(2)-macroglobulin was the tetramer, whereas its dimer was detectable in patients with high serum levels of alpha(2)-macroglobulin. The serum alpha(2)-macroglobulin concentration was not associated with glycated hemoglobin or any other glycemic variable as evaluated from 48-h continuous glucose monitoring, but showed close correlation with left ventricular posterior wall thickness, carotid artery intima-media thickness, urinary albumin:creatinine ratio (ACR) and brachial-ankle pulse wave velocity (baPWV). Multivariate analysis revealed only the ACR and baPWV to be independent variables influencing serum levels of alpha(2)-macroglobulin. Thus, an increased ACR and baPWV are associated with higher serum concentrations of alpha(2)-macroglobulin, and the latter may contribute to the mechanism by which albuminuria increases the risk of developing cardiovascular diseases.