尿液细胞外囊泡的蛋白质组学特征鉴定出AGP1作为原发性醛固酮增多症的潜在生物标志物。
Proteomic Profile of Urinary Extracellular Vesicles Identifies AGP1 as a Potential Biomarker of Primary Aldosteronism.
作者信息
Barros Eric R, Rigalli Juan Pablo, Tapia-Castillo Alejandra, Vecchiola Andrea, Young Morag J, Hoenderop Joost G J, Bindels René J M, Fardella Carlos E, Carvajal Cristian A
机构信息
Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, HB Nijmegen, The Netherlands.
出版信息
Endocrinology. 2021 Apr 1;162(4). doi: 10.1210/endocr/bqab032.
CONTEXT
Primary aldosteronism (PA) represents 6% to 10% of all essential hypertension patients and is diagnosed using the aldosterone-to-renin ratio (ARR) and confirmatory studies. The complexity of PA diagnosis encourages the identification of novel PA biomarkers. Urinary extracellular vesicles (uEVs) are a potential source of biomarkers, considering that their cargo reflects the content of the parent cell.
OBJECTIVE
We aimed to evaluate the proteome of uEVs from PA patients and identify potential biomarker candidates for PA.
METHODS
Second morning spot urine was collected from healthy controls (n = 8) and PA patients (n = 7). The uEVs were isolated by ultracentrifugation and characterized. Proteomic analysis on uEVs was performed using LC-MS Orbitrap.
RESULTS
Isolated uEVs carried extracellular vesicle markers, showed a round shape and sizes between 50 and 150 nm. The concentration of uEVs showed a direct correlation with urinary creatinine (r = 0.6357; P = 0.0128). The uEV size mean (167 ± 6 vs 183 ± 4nm) and mode (137 ± 7 vs 171 ± 11nm) was significantly smaller in PA patients than in control subjects, but similar in concentration. Proteomic analysis of uEVs from PA patients identified an upregulation of alpha-1-acid glycoprotein 1 (AGP1) in PA uEVs, which was confirmed using immunoblot. A receiver operating characteristic curve analysis showed an area under the curve of 0.92 (0.82 to 1; P = 0.0055).
CONCLUSION
Proteomic and further immunoblot analyses of uEVs highlights AGP1 as potential biomarker for PA.
背景
原发性醛固酮增多症（PA）占所有原发性高血压患者的6%至10%，通过醛固酮与肾素比值（ARR）及确诊性检查进行诊断。PA诊断的复杂性促使人们寻找新的PA生物标志物。尿细胞外囊泡（uEVs）是生物标志物的潜在来源，因为其内含物反映了母细胞的成分。
目的
我们旨在评估PA患者uEVs的蛋白质组，并鉴定PA潜在的生物标志物候选物。
方法
收集健康对照者（n = 8）和PA患者（n = 7）的次日晨尿。通过超速离心分离uEVs并进行表征。使用液相色谱-质谱联用仪（LC-MS Orbitrap）对uEVs进行蛋白质组分析。
结果
分离出的uEVs携带细胞外囊泡标志物，呈圆形，大小在50至150纳米之间。uEVs的浓度与尿肌酐呈直接相关（r = 0.6357；P = 0.0128）。PA患者uEVs的大小均值（167±6 vs 183±4纳米）和众数（137±7 vs 171±11纳米）显著小于对照者，但浓度相似。对PA患者uEVs的蛋白质组分析发现，PA的uEVs中α-1-酸性糖蛋白1（AGP1）上调，通过免疫印迹法得以证实。受试者工作特征曲线分析显示曲线下面积为0.92（0.82至1；P = 0.0055）。
结论
对uEVs进行蛋白质组及进一步免疫印迹分析突出了AGP1作为PA潜在生物标志物的作用。
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