Disease-specific signatures of circulating extracellular vesicles detected by the surface plasmon resonance imaging: a pilot study

Tatsuki Shibuta , Yukichi Takada , Shiori Nishinosono , Seiko Yasuda , Yasuhiro Ono , Yoshitaka Hirooka , Daisuke Irikura , Kensuke Saito , Tsukuru Umemura

Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (1) : 36 -53.

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Extracellular Vesicles and Circulating Nucleic Acids ›› 2025, Vol. 6 ›› Issue (1) :36 -53. DOI: 10.20517/evcna.2024.82
Original Article

Disease-specific signatures of circulating extracellular vesicles detected by the surface plasmon resonance imaging: a pilot study

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Abstract

Aim: 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.

Methods: Using surface plasmon resonance imaging (SPRi), we analyzed EVs surface molecules and identified circulating EVs in healthy controls (n = 18), patients with type 2 diabetes mellitus (T2DM; n = 71), and those with hypertension (HT; n = 47).

Results: 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.

Conclusion: Our findings demonstrate that profiling of circulating EVs via the SPRi method offers a novel approach for diagnosing and monitoring human diseases.

Keywords

Extracellular vesicles / surface plasmon resonance imaging / diabetes / hypertension / blood cell

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Tatsuki Shibuta, Yukichi Takada, Shiori Nishinosono, Seiko Yasuda, Yasuhiro Ono, Yoshitaka Hirooka, Daisuke Irikura, Kensuke Saito, Tsukuru Umemura. Disease-specific signatures of circulating extracellular vesicles detected by the surface plasmon resonance imaging: a pilot study. Extracellular Vesicles and Circulating Nucleic Acids, 2025, 6(1): 36-53 DOI:10.20517/evcna.2024.82

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References

[1]

Witwer KW,Bemis LT.Standardization of sample collection, isolation and analysis methods in extracellular vesicle research.J Extracell Vesicles2013;2:20360 PMCID:PMC3760646

[2]

Shah R,Freedman JE.Circulating extracellular vesicles in human disease.N Engl J Med2018;379:958-66

[3]

Cable J,Coffey RJ.Exosomes, microvesicles, and other extracellular vesicles-a Keystone Symposia report.Ann N Y Acad Sci2023;1523:24-37 PMCID:PMC10715677

[4]

Castaño C,Párrizas M.An overview of inter-tissue and inter-kingdom communication mediated by extracellular vesicles in the regulation of mammalian metabolism.Int J Mol Sci2023;24:2071 PMCID:PMC9916451

[5]

Nation GK,Pua HH.Secret messengers: extracellular RNA communication in the immune system.Immunol Rev2021;304:62-76 PMCID:PMC8756459

[6]

Phillips W,Hill AF.Understanding extracellular vesicle and nanoparticle heterogeneity: novel methods and considerations.Proteomics2021;21:e2000118 PMCID:PMC8365743

[7]

Hermann S,Kirchner B.Transcriptomic profiling of cell-free and vesicular microRNAs from matched arterial and venous sera.J Extracell Vesicles2019;8:1670935 PMCID:PMC6781181

[8]

Yang D,Wu H.Determination of high-affinity antibody-antigen binding kinetics using four biosensor platforms.J Vis Exp2017;122:55659 PMCID:PMC5564993

[9]

Gool EL,Schasfoort RBM.Surface plasmon resonance is an analytically sensitive method for antigen profiling of extracellular vesicles.Clin Chem2017;63:1633-41

[10]

Rikkert LG,van Dam A.Detection of extracellular vesicles in plasma and urine of prostate cancer patients by flow cytometry and surface plasmon resonance imaging.PLoS One2020;15:e0233443 PMCID:PMC7272016

[11]

Tallon C,Yoo SW.Inhibition of neutral sphingomyelinase 2 reduces extracellular vesicle release from neurons, oligodendrocytes, and activated microglial cells following acute brain injury.Biochem Pharmacol2021;194:114796 PMCID:PMC8919377

[12]

Yamasaki T,Nakano S.Development of a surface plasmon resonance-based immunosensor for detection of 10 major O-antigens on Shiga toxin-producing escherichia coli, with a gel displacement technique to remove bound bacteria.Anal Chem2016;88:6711-7

[13]

Ito T,Kumagai Y.Quantitative analysis of interaction between CADM1 and its binding cell-surface proteins using surface plasmon resonance imaging.Front Cell Dev Biol2018;6:86 PMCID:PMC6090299

[14]

Szymanska B,Oldak L,Hermanowicz-Szamatowicz K.Two biosensors for the determination of interleukin-6 in blood plasma by array SPRi.Biosensors2022;12:412 PMCID:PMC9221503

[15]

Zielinska Z,Kacperczyk-Bartnik J.An array SPRi biosensor for the determination on PARP-1 in blood plasma.Biomedicines2023;11:602 PMCID:PMC9953221

[16]

Oldak L,Żelazowska-Rutkowska B.Two SPRi biosensors for the determination of cathepsin S in blood plasma.Talanta2021;225:121900

[17]

Liang K,Fan J.Nanoplasmonic quantification of tumor-derived extracellular vesicles in plasma microsamples for diagnosis and treatment monitoring.Nat Biomed Eng2017;1:0021 PMCID:PMC5543996

[18]

Liu C,An Z.Sensitive detection of exosomal proteins via a compact surface plasmon resonance biosensor for cancer diagnosis.ACS Sens2018;3:1471-9 PMCID:PMC8628517

[19]

Das S,Gartia MR.Surface plasmon resonance (SPR) sensor for cancer biomarker detection.Biosensors2023;13:396 PMCID:PMC10046379

[20]

Baltazar JM, Gu W, Yu Q. Enhancing extracellular vesicle detection via cotargeting tetraspanin biomarkers.Anal Chem2024;96:16406-14

[21]

Picciolini S,Carlomagno C.An SPRi-based biosensor pilot study: analysis of multiple circulating extracellular vesicles and hippocampal volume in Alzheimer’s disease.J Pharm Biomed Anal2021;192:113649

[22]

Brealey J,Tempest R.Shining a light on fluorescent EV dyes: evaluating efficacy, specificity and suitability by nano-flow cytometry.J Extracell Biol2024;3:e70006 PMCID:PMC11465455

[23]

Yaraki M, Tukova A, Wang Y. Emerging SERS biosensors for the analysis of cells and extracellular vesicles.Nanoscale2022;14:15242-68

[24]

Zhu L,Cui J.Label-free quantitative detection of tumor-derived exosomes through surface plasmon resonance imaging.Anal Chem2014;86:8857-64 PMCID:PMC4151789

[25]

Li Y,Li Q.EV-origin: enumerating the tissue-cellular origin of circulating extracellular vesicles using exLR profile.Comput Struct Biotechnol J2020;18:2851-9 PMCID:PMC7588739

[26]

2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021.Lancet2023;402:203-34 PMCID:PMC10364581

[27]

Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants.Lancet2021;398:957-80 PMCID:PMC8446938

[28]

Arauna D,Padró T,Palomo I.Frail older adults show a distinct plasma microvesicle profile suggesting a prothrombotic and proinflammatory phenotype.J Cell Physiol2021;236:2099-108

[29]

Jansen F,Pfeifer A.Endothelial- and immune cell-derived extracellular vesicles in the regulation of cardiovascular health and disease.JACC Basic Transl Sci2017;2:790-807 PMCID:PMC6059011

[30]

Araki E,Kondo T.Japanese clinical practice guideline for diabetes 2019.J Diabetes Investig2020;11:1020-76 PMCID:PMC7378414

[31]

Shimamoto K, Ando K, Fujita T, et al; Japanese Society of Hypertension Committee for Guidelines for the Management of Hypertension. The Japanese Society of Hypertension Guidelines for the management of hypertension (JSH 2014). Hypertens Res. 2014;37:253-390.

[32]

Umemura S,Arima S.The Japanese Society of Hypertension Guidelines for the management of hypertension (JSH 2019).Hypertens Res2019;42:1235-481

[33]

Haneda M, Utsunomiya K, Koya D, et al; Joint Committee on Diabetic Nephropathy. A new classification of diabetic nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy. J Diabetes Investig. 2015;6:242-6. PMCID:PMC4364860

[34]

Harada A, Ueshima H, Kinoshita Y, et al; Japan Arteriosclerosis Longitudinal Study Group. Absolute risk score for stroke, myocardial infarction, and all cardiovascular disease: Japan Arteriosclerosis Longitudinal Study. Hypertens Res. 2019;42:567-79.

[35]

Wang WC.The immobilized leukoagglutinin from the seeds of Maackia amurensis binds with high affinity to complex-type Asn-linked oligosaccharides containing terminal sialic acid-linked alpha-2,3 to penultimate galactose residues.J Biol Chem1988;263:4576-85

[36]

Laurent LC,Adelson PD.Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH extracellular RNA communication consortium.J Extracell Vesicles2015;4:26533 PMCID:PMC4553263

[37]

Yates AG,Erdbrügger U.In sickness and in health: the functional role of extracellular vesicles in physiology and pathology in vivo: Part I: health and normal physiology.J Extracell Vesicles2022;11:e12151 PMCID:PMC8765331

[38]

Yates AG,Erdbrügger U.In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part II: Pathology.J Extracell Vesicles2022;11:e12190 PMCID:PMC8765328

[39]

Andreu Z.Tetraspanins in extracellular vesicle formation and function.Front Immunol2014;5:442 PMCID:PMC4165315

[40]

Teng F.Shedding light on extracellular vesicle biogenesis and bioengineering.Adv Sci2020;8:2003505 PMCID:PMC7788585

[41]

Gurung S,Touramanidou L.The exosome journey: from biogenesis to uptake and intracellular signalling.Cell Commun Signal2021;19:47 PMCID:PMC8063428

[42]

Shimaoka M,Gaowa A,Park EJ.Connexins and integrins in exosomes.Cancers2019;11:106 PMCID:PMC6356207

[43]

Brosseau C,Magnan A.CD9 tetraspanin: a new pathway for the regulation of inflammation?.Front Immunol2018;9:2316 PMCID:PMC6189363

[44]

Cho JH,Dimri GP.MicroRNA-31 is a transcriptional target of histone deacetylase inhibitors and a regulator of cellular senescence.J Biol Chem2015;290:10555-67 PMCID:PMC4400362

[45]

Ross R.Atherosclerosis--an inflammatory disease.N Engl J Med1999;340:115-26

[46]

Barger AC,Lainey LL.Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis.N Engl J Med1984;310:175-7

[47]

Chen D,Liu P.Adventitial vasa vasorum neovascularization in femoral artery of type 2 diabetic patients with macroangiopathy is associated with macrophages and lymphocytes as well as the occurrence of cardiovascular events.Thromb Haemost2023;123:989-98

[48]

Smith MJ,Cambier JC.B cells in type 1 diabetes mellitus and diabetic kidney disease.Nat Rev Nephrol2017;13:712-20 PMCID:PMC6733025

[49]

Choudhary N.Interleukin-6 and C-reactive protein in pathogenesis of diabetic nephropathy: new evidence linking inflammation, glycemic control, and microalbuminuria.Iran J Kidney Dis2008;2:72-9

[50]

Kuo CS,Hsu CY.Increased activin A levels in prediabetes and association with carotid intima-media thickness: a cross-sectional analysis from I-Lan Longitudinal Aging Study.Sci Rep2018;8:9957 PMCID:PMC6028626

[51]

Ueland T,Aakhus S.Activin A and cardiovascular disease in type 2 diabetes mellitus.Diab Vasc Dis Res2012;9:234-7

[52]

Peng LN,Liang CK.Association between serum activin A and metabolic syndrome in older adults: potential of activin A as a biomarker of cardiometabolic disease.Exp Gerontol2018;111:197-202

[53]

Yndestad A,Øie E.Elevated levels of activin A in heart failure: potential role in myocardial remodeling.Circulation2004;109:1379-85

[54]

Robson NC,McAlpine T,Cebon J.Activin-A attenuates several human natural killer cell functions.Blood2009;113:3218-25

[55]

Shiozaki M,Eto Y.Activin A: a commitment factor in erythroid differentiation.Biochem Biophys Res Commun1998;242:631-5

[56]

Kaushansky K.Thrombopoietin and its receptor in normal and neoplastic hematopoiesis.Thromb J2016;14:40 PMCID:PMC5056461

[57]

Bosco O,Gruden G.Thrombopoietin contributes to enhanced platelet activation in patients with type 1 diabetes mellitus.Int J Mol Sci2021;22:7032 PMCID:PMC8269076

[58]

Pretorius L,Adams RCM,Laubscher WA.Platelet activity and hypercoagulation in type 2 diabetes.Cardiovasc Diabetol2018;17:141 PMCID:PMC6214175

[59]

Rossi F,Pareti FI,Tremoli E.In vitro measurement of platelet glycoprotein IIb/IIIa receptor blockade by abciximab: interindividual variation and increased platelet secretion.Haematologica2001;86:192-8

[60]

Kawabata H.Transferrin and transferrin receptors update.Free Radic Biol Med2019;133:46-54

[61]

Larsen SB,Hvas AM.Platelet turnover in stable coronary artery disease - influence of thrombopoietin and low-grade inflammation.PLoS One2014;9:e85566 PMCID:PMC3897460

[62]

Prattichizzo F,Sabbatinelli J.CD31+ extracellular vesicles from patients with type 2 diabetes shuttle a miRNA signature associated with cardiovascular complications.Diabetes2021;70:240-54

[63]

Jaskuła K,Gaciong Z.Cardiovascular effects mediated by HMMR and CD44.Mediators Inflamm2021;2021:4977209 PMCID:PMC8286199

[64]

Kodama K,Toda K.Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes.Proc Natl Acad Sci U S A2012;109:7049-54 PMCID:PMC3344989

[65]

Khan AI,Heit B.Role of CD44 and hyaluronan in neutrophil recruitment.J Immunol2004;173:7594-601

[66]

McKee CM,Cowman M.Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44.J Clin Invest1996;98:2403-13 PMCID:PMC507693

[67]

Collura S,Morsiani C.MicroRNA profiles of human peripheral arteries and abdominal aorta in normal conditions: microRNAs-27a-5p, -139-5p and -155-5p emerge and in atheroma too.Mech Ageing Dev2021;198:111547

[68]

Lu Y,Feng Q.Diabetic nephropathy: perspective on extracellular vesicles.Front Immunol2020;11:943 PMCID:PMC7283536

[69]

Howes RE,Piel FB.The global distribution of the Duffy blood group.Nat Commun2011;2:266 PMCID:PMC3074097

[70]

Gencer S,Aslani M,Döring Y.Atypical chemokine receptors in cardiovascular disease.Thromb Haemost2019;119:534-41

[71]

Betterman KL.Decoys and cardiovascular development: CXCR7 and regulation of adrenomedullin signaling.Dev Cell2014;30:490-1

[72]

Torphy RJ,Schulick RD.Atypical chemokine receptors: emerging therapeutic targets in cancer.Trends Pharmacol Sci2022;43:1085-97 PMCID:PMC9669249

[73]

Forejtnikovà H,Zermati Y.Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis.Blood2010;116:5357-67

[74]

Vance S,Henrich VC.Comparative analysis of human growth hormone in serum using SPRi, nano-SPRi and ELISA assays.J Vis Exp2016;107:53508 PMCID:PMC4781177

[75]

Hauss WH,Schulte H.Adrenaline and noradrenaline as possible chemical mediators in the pathogenesis of arteriosclerosis.Ann N Y Acad Sci1990;598:91-101

[76]

Reznikova MB,Postnov YuV.Erythrocyte membrane sialic acids in primary and secondary hypertension in man and rat.Eur J Clin Invest1984;14:87-9

[77]

Hisamatsu T,Kadota A,Arima H.Epidemiology of hypertension in Japan: beyond the new 2019 Japanese guidelines.Hypertens Res2020;43:1344-51

[78]

Hosseinkhani B,D'Haen J.Direct detection of nano-scale extracellular vesicles derived from inflammation-triggered endothelial cells using surface plasmon resonance.Nanomedicine2017;13:1663-71

[79]

Hirschberg Y,Schildermans K.Characterising extracellular vesicles from individual low volume cerebrospinal fluid samples, isolated by SmartSEC.J Extracell Biol2022;1:e55 PMCID:PMC11080878

[80]

Welsh JA, Goberdhan DCI, O'Driscoll L, et al; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404. PMCID:PMC10850029

[81]

Cvjetkovic A,Lässer C.The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles.J Extracell Vesicles2014;3:23111 PMCID:PMC3967015

[82]

Xie J,Haesebrouck F,Vandenbroucke RE.The tremendous biomedical potential of bacterial extracellular vesicles.Trends Biotechnol2022;40:1173-94

[83]

Sun G,Zheng J,Cheng T.Emerging roles of extracellular vesicles in normal and malignant hematopoiesis.J Clin Invest2022;132:e160840 PMCID:PMC9479752

[84]

Buzas EI.The roles of extracellular vesicles in the immune system.Nat Rev Immunol2023;23:236-50 PMCID:PMC9361922

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