Shibuta Tatsuki, Takada Yukichi, Nishinosono Shiori, Yasuda Seiko, Ono Yasuhiro, Hirooka Yoshitaka, Irikura Daisuke, Saito Kensuke, Umemura Tsukuru
Department of Medical Technology and Sciences, International University of Health and Welfare, Fukuoka 831-8501, Japan.
Department of Diabetes and Metabolism, Kouhoukai Takagi Hospital, Fukuoka 831-0016, Japan.
Extracell Vesicles Circ Nucl Acids. 2025 Feb 11;6(1):36-53. doi: 10.20517/evcna.2024.82. eCollection 2025.
Cells in the human body release extracellular vesicles (EVs) into fluids, such as plasma, urine, and cerebrospinal fluid. EVs express tetraspanin family proteins (e.g., CD63, CD9, and CD81) and cell-specific antigens on their surface as common and specific markers, respectively. In this study, we hypothesized that the profile of blood cell-derived circulating EVs could reveal both common and specific pathophysiology in atherogenic diseases. Using surface plasmon resonance imaging (SPRi), we analyzed EVs surface molecules and identified circulating EVs in healthy controls ( = 18), patients with type 2 diabetes mellitus (T2DM; = 71), and those with hypertension (HT; = 47). Patients with T2DM and HT exhibited distinct EV profiles: (i) CD9, CD110, CD20, activin receptor type-2A (AcvRIIA), Duffy antigen receptor for chemokine, and CD44 positive EVs were upregulated in T2DM; (ii) CD9, Maackia amurensis agglutinin lectin binding molecules (MBM), CD20, AcvRIIA, and CD44 positive EVs were upregulated in HT. By analyzing an appropriate set of three antigens or using dimensional reduction clustering, we were able to clearly differentiate between T2DM, HT, and control groups. In some patients, disease severity correlated with CD44 and CD20 in T2DM and MBM and AcvRIIA in HT. Our findings demonstrate that profiling of circulating EVs via the SPRi method offers a novel approach for diagnosing and monitoring human diseases.
人体细胞会向血浆、尿液和脑脊液等体液中释放细胞外囊泡（EVs）。EVs分别在其表面表达四跨膜蛋白家族蛋白（如CD63、CD9和CD81）以及细胞特异性抗原作为常见标记和特异性标记。在本研究中，我们假设血细胞来源的循环EVs的特征可以揭示动脉粥样硬化性疾病中常见和特定的病理生理学。我们使用表面等离子体共振成像（SPRi）分析了EVs的表面分子，并鉴定了健康对照者（n = 18）、2型糖尿病（T2DM；n = 71）患者和高血压（HT；n = 47）患者的循环EVs。T2DM和HT患者表现出不同的EVs特征：（i）T2DM患者中CD9、CD110、CD20、激活素受体2A型（AcvRIIA）、趋化因子达菲抗原受体和CD44阳性的EVs上调；（ii）HT患者中CD9、黑荆凝集素结合分子（MBM）、CD20、AcvRIIA和CD44阳性的EVs上调。通过分析一组合适的三种抗原或使用降维聚类，我们能够清楚地区分T2DM、HT和对照组。在一些患者中，疾病严重程度与T2DM中的CD44和CD20以及HT中的MBM和AcvRIIA相关。我们的研究结果表明，通过SPRi方法对循环EVs进行分析为人类疾病的诊断和监测提供了一种新方法。
