Journal of extracellular biology最新文献

{"title":"Extracellular Vesicle Surface Protein Profiling in Metabolic Dysfunction-associated Steatotic Liver Disease in Obesity","authors":"Nahuel Aquiles Garcia,&nbsp;Kirstine Kløve-Mogensen,&nbsp;Katja Lund Cliff,&nbsp;Rikke Bæk,&nbsp;Malwina Ulanowska,&nbsp;Javier Alejandro Donoso Quezada,&nbsp;Malene Møller Jørgensen,&nbsp;Aase Handberg,&nbsp;Maiken Mellergaard","doi":"10.1002/jex2.70183","DOIUrl":"10.1002/jex2.70183","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in obesity, but scalable tools for biological risk stratification remain limited. In this cross-sectional, single-centre discovery study (MULTISITE), we profiled circulating extracellular vesicle (cEV) surface proteins by EV Array in platelet-poor plasma from individuals with obesity and MASLD (<i>n</i> = 36), individuals with obesity without MASLD (<i>n</i> = 24), and lean controls (<i>n</i> = 27). Liver fat was quantified by magnetic resonance imaging proton density fat fraction (MRI-PDFF). We assessed group differences, associations with continuous PDFF, and exploratory discriminatory performance using single markers, pairwise ratios, and sparse logistic models. We also performed an exploratory PDFF-extremes enrichment analysis within obesity by comparing the top versus bottom 30% of the PDFF distribution (<i>n</i> = 18 vs. <i>n</i> = 18), excluding the middle 40%. Across contrasts, single markers showed modest separation, whereas pairwise ratios provided stronger exploratory signals. In the discovery panel, uncorrected best-ratio AUCs were 0.80–0.84 and sparse-model AUCs were 0.79–0.84 under internal, non-nested cross-validation across MASLD-focused contrasts. In the focused panel, CD36 and TREM2 were the strongest single-marker signals for MASLD versus lean controls, whereas LRP-1-anchored ratios captured obesity- and liver fat-associated patterns. In the PDFF-extremes analysis, internally cross-validated AUCs reached 0.87–0.89 in the discovery panel and 0.86 for LRP-1/FATP5 in the focused panel; these estimates should be interpreted as exploratory, uncorrected discovery-stage observations rather than validated classifier performance. Exploratory benchmarking showed that FLI, but not FIB-4, discriminated MASLD-related contrasts strongly, however, these analyses provide contextual benchmarking only and do not establish incremental clinical value of cEV markers beyond routine clinical predictors. These findings nominate biologically coherent cEV surface signatures for future validation in MASLD, anchored by lipid handling/scavenger pathways and complemented by stress, immune, and coagulation biology.</p><p><b>Trial Registration</b>: ClinicalTrials.gov: NCT05699863</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148876860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Method Matters: A Proteomics-Informed Framework for Selecting Extracellular Vesicle Isolation Methods for Plasma","authors":"Scheila Julia Werle,&nbsp;Marie Louise Nautrup Therkelsen,&nbsp;Chen Meng,&nbsp;Mads Grønborg,&nbsp;Lise Lotte Gluud,&nbsp;Dres Damgaard","doi":"10.1002/jex2.70180","DOIUrl":"https://doi.org/10.1002/jex2.70180","url":null,"abstract":"<p>Extracellular vesicles (EVs) hold significant promise as biomarkers, but their clinical application is constrained by variability in pre-analytical handling and isolation. EV isolation methods directly shape which plasma-derived EV-containing preparations are captured, yet systematic method comparisons across multiple analytical dimensions are limited. We comprehensively evaluated eleven EV isolation methods in pooled platelet-poor plasma (5 donors; 6 technical replicates/method). We further evaluated selected methods using five individual donors. EVs were quantified by NanoFCM, profiled for tetraspanins (CD9, CD63, CD81) via MSD assays, and further characterized by LC-MS/MS proteomics. We show that different EV isolation methods for plasma produce different EV containing preparation. EV isolation methods broadened proteome coverage in plasma but showed divergent performance. While all methods captured EVs in the 50–150 nm range, centrifugation and ultracentrifugation identified the broadest proteomes (up to 1093 proteins) driven by higher plasma protein carryover. Conversely, ExoEasy and qEV 70 isolated larger EVs and achieved stronger depletion of abundant plasma proteins but showed lower proteome coverage. A total of 117 proteins were detected across all isolation methods. Pre-clearing of samples removed contaminants but at the cost of protein identifications. We demonstrate that method selection must align with the specific analytical goal: centrifugation for comprehensive proteome profiling, affinity/size-exclusion methods for contaminant-sensitive assays, and precipitation for high-throughput applications. This systematic characterization provides an evidence-based framework and look-up resource for matching isolation strategies to downstream applications and research questions.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles","authors":"Marzena Kurzawa-Akanbi,&nbsp;Jennifer Haggarty,&nbsp;Carina Hansohn,&nbsp;Mohamed T. Patel,&nbsp;Angela J. Cree,&nbsp;Peisi Teo,&nbsp;Milly Armstrong,&nbsp;Nathan Coles,&nbsp;Mark Platt,&nbsp;Helen Griffiths,&nbsp;Heather J. Cordell,&nbsp;Ahmad Khundakar,&nbsp;Pola Goldberg Oppenheimer,&nbsp;Phillip Whitfield,&nbsp;Andrew Lotery,&nbsp;Henning Urlaub,&nbsp;Sina Mozaffari-Jovin,&nbsp;Majlinda Lako","doi":"10.1002/jex2.70178","DOIUrl":"https://doi.org/10.1002/jex2.70178","url":null,"abstract":"<p>Vision impairment caused by age-related macular degeneration (AMD) is a global health priority. Retinal pathology is driven by ageing and exacerbated by genetic and environmental risk factors. Peripheral blood circulation is increasingly recognised as a contributor to disease initiation and progression, and a source of biomarkers to support earlier diagnosis and personalised treatment strategies. Here, we performed an analysis of plasma-derived extracellular vesicle (EV)-enriched samples from 30 AMD and 30 controls. Proteomics identified significantly altered proteins in AMD, the majority of which were downregulated with a strong interaction network involving complement proteins and endopeptidase inhibitors. Importantly, many of the altered proteins are known AMD biomarker candidates and act in pathways affecting AMD: oxidative stress response, immune function and proteolysis dysregulation. Lipidomics revealed an increase in total sphingomyelin to ceramide ratio in AMD, indicating lipid metabolism defects. Raman spectroscopy complemented these findings by demonstrating protein and lipid oxidative modifications, alongside compositional abnormalities in AMD samples. Thus, AMD plasma EV-enriched samples carry a systemic signature of complement and coagulation dysregulation, impaired redox homeostasis, and altered sphingolipid metabolism, reflecting established mechanisms of AMD retinal pathology. These AMD-associated biochemical profiles form a promising source for developing new diagnostics and mechanistic insights for precision medicine.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148848928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Piezo1-Mediated Calcium Signalling for Enhanced Extracellular Vesicle Biogenesis and Cargo Loading","authors":"Najla A. Saleh,&nbsp;Rozita Shafiq,&nbsp;Amanda P. Cicerone,&nbsp;Sadhana Kilangodi,&nbsp;Hayden Hartwig,&nbsp;George I. Mias,&nbsp;Guangqing Lu,&nbsp;Jun R. Huh,&nbsp;Weiping Li,&nbsp;Cheri X. Deng,&nbsp;Masamitsu Kanada","doi":"10.1002/jex2.70182","DOIUrl":"https://doi.org/10.1002/jex2.70182","url":null,"abstract":"<p>Cell-derived extracellular vesicles (EVs) are promising nanocarriers for therapeutic delivery platforms owing to their biocompatibility and capacity to protect and efficiently transport bioactive molecules. However, EV-based therapeutics remain constrained by inefficient cargo loading and low production yields, which limit scalable biomanufacturing. To overcome these limitations, we exploited the use of the mechanosensitive ion channel Piezo1 as a robust regulator of EV biogenesis using HEK293FT cells co-transfected with Piezo1 and the bioluminescent EV reporter PalmReNL. Activation of Piezo1 with Yoda1 (30 µM) increased PalmReNL-EV release by 3-fold, while GsMTx4 inhibited EV release by 80.7%. This effect was unaffected by removal of extracellular Ca²⁺ but was suppressed by intracellular Ca²⁺ chelation with BAPTA-AM, indicating a reliance on intracellular Ca²⁺ mobilisation. Small EVs (sEVs) from Piezo1-activated cells were purified by anion exchange chromatography and analysed by proteomics, identifying 48 proteins exclusively in Piezo1-induced sEVs preparations among 148 total detected, including cytoskeletal and stress-related factors, while preserving enrichment of extracellular matrix (ECM) structural components prominent in both conditions. Yoda1 treatment increased the release of both large EVs (lEVs) and sEVs, with a particularly pronounced increase in sEV production. As a proof of concept for therapeutic cargo delivery, Yoda1 stimulation increased the incorporation of exogenously expressed interleukin-10 (IL-10) into sEVs by up to 4-fold, and the bioactivity of sEV-associated IL-10 was validated using IL-10-CyCLoPs reporter cells. However, exposing Piezo1-overexpressing cells to 30 µM Yoda1 markedly delayed cell adhesion and spreading, indicating that excessive Piezo1 activation may constrain sustained production of therapeutic sEVs. Collectively, these results identify mechanotransduction as a key regulator of sEV biogenesis and underscore the need for precise temporal control, potentially achievable through ultrasound-based modulation, for the rational engineering of next-generation sEV therapeutics.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calpeptin Reduces Extracellular Vesicle Secretion and Induces Anti-Inflammatory Effects but Upregulates HO-1 and Alters Adiponectin Levels in Human Adipocytes","authors":"Johanna Matilainen,&nbsp;Sanni Foster,&nbsp;Viivi Berg,&nbsp;Janne Tampio,&nbsp;Tanja Turunen,&nbsp;Anne-Mari Mustonen,&nbsp;Heikki Kyykallio,&nbsp;Maija Vaittinen,&nbsp;Ville Männistö,&nbsp;Jussi Pihlajamäki,&nbsp;Marjo Malinen,&nbsp;Sanna Oikari,&nbsp;Pirjo Käkelä,&nbsp;Dorota Kaminska,&nbsp;Veera Luukkonen,&nbsp;Kristiina M. Huttunen,&nbsp;Martin Wabitsch,&nbsp;Petteri Nieminen,&nbsp;Kirsi Rilla","doi":"10.1002/jex2.70177","DOIUrl":"https://doi.org/10.1002/jex2.70177","url":null,"abstract":"<p>Recent studies have shown that adipose tissue (AT) secretes elevated levels of extracellular vesicles (EVs) in obesity, and these EVs play roles in metabolic diseases. The inhibition of calpains has anti-inflammatory and anti-fibrotic effects on AT in mice and reduces EV secretion in some cell types in vitro. However, its effects on human AT and adipocyte EV secretion remain unexplored. This study aimed to investigate calpeptin's effects on EV-mediated communication and adipocyte function, offering potential insights into therapeutic approaches for metabolic diseases. Human Simpson Golabi Behmel Syndrome (SGBS) preadipocytes were differentiated and treated with calpeptin. EVs were isolated by standard ultracentrifugation, and studied by nanoparticle tracking analysis, electron microscopy, and mass spectrometry. Diverse analyses, including RNA-sequencing, liquid chromatography–mass spectrometry (LC–MS), and confocal microscopy were utilized to study calpeptin's effects on SGBS cells. AT samples from bariatric surgery patients were cultured ex vivo to assess calpeptin's effects on primary AT. We demonstrated for the first time that calpeptin reduces EV secretion in human SGBS adipocytes. Proteomic analyses revealed that calpeptin alters the abundances of proteins related to EV secretory pathways. While reduced EV secretion was accompanied by anti-inflammatory effects, calpeptin also altered insulin signalling pathways and reduced adiponectin expression, suggesting negative effects on adipocyte metabolism. Indeed, LC–MS analyses of cells and EVs revealed that calpeptin altered proteins—both in cells and EVs—that are associated with stress responses. Notably, calpeptin upregulated HO-1 in vitro and in ex vivo AT cultures, indicating induced oxidative stress in adipocytes and AT. While calpeptin shows anti-inflammatory promise in human SGBS adipocytes, its adverse effects on insulin signalling, adiponectin expression, and signs of oxidative stress raise concerns about its therapeutic potential against obesity-related pathologies in humans. Our results highlight the need to understand the broader impact of calpeptin on adipocyte metabolism.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GW4869 Depletes Macrophages and Increases Number of Extracellular Vesicles in Murine Peritoneal Cavity Fluid","authors":"Johann Mar Gudbergsson,&nbsp;Pedro Henrique Gobira,&nbsp;Rodrigo Grassi-Oliveira,&nbsp;Anders Etzerodt","doi":"10.1002/jex2.70169","DOIUrl":"https://doi.org/10.1002/jex2.70169","url":null,"abstract":"<p>Pharmacological strategies to modulate extracellular vesicle (EV) release in vivo are gaining traction, yet their broader effects on local immune microenvironments remain unclear. In this study, we assessed how repeated intraperitoneal (i.p.) dosing of the neutral sphingomyelinase inhibitor GW4869 reshapes the peritoneal cavity. GW4869 administration triggered a strong local inflammatory reaction, was accompanied by a selective depletion of resident peritoneal macrophages and was associated with higher EV counts 24 h after the final injection. Targeted macrophage depletion in the absence of GW4869 produced a comparable increase in EV levels, implicating shifts in cellular composition and inflammatory state as key drivers of EV accumulation. By applying single-particle flow cytometry, we differentiated small EV subsets from ApoB+ lipoproteins and uncovered substantial heterogeneity within CD9+ particles, ruling out lipoprotein co-detection as the main explanation for the elevated EV signal. Overall, our results highlight that GW4869 treatment can reshape the local immune landscape and that such context-dependent changes must be considered when using this compound to infer EV biogenesis in vivo.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 9","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle-Based miRNA Profiling in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Secondary Analysis of the MULTISITE Clinical Trial","authors":"Katja Lund Cliff,&nbsp;Dominic Guanzon,&nbsp;Andrew Lai,&nbsp;Katherin Scholz-Romero,&nbsp;Gunna Christiansen,&nbsp;Aase Handberg,&nbsp;Carlos Salomon,&nbsp;Maiken Mellergaard","doi":"10.1002/jex2.70173","DOIUrl":"https://doi.org/10.1002/jex2.70173","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the worldwide leading cause of liver-related mortality with a prevalence of 75% among individuals with obesity and lacking screenings tools. Extracellular vesicles (EVs)-based microRNAs (miRNAs) have emerged as promising biomarkers with important roles in the pathogenesis of MASLD. This study aimed to characterize EV-based miRNA profiles in individuals with obesity and MASLD before and during weight loss intervention. Small RNA sequencing was used to profile EV-miRNAs from plasma across three groups: individuals with obesity and MASLD (<i>n</i> = 35), individuals with obesity without hepatic steatosis (<i>n</i> = 24) and lean controls without hepatic steatosis (<i>n</i> = 26). Further, the MASLD group underwent a personalized weight-loss intervention. The liver and MASLD-related miR-122-5p and three other miRNAs were differentially expressed in the MASLD group compared with the obesity control group at baseline. Moreover, miR-122-5p correlated with liver fat and liver enzymes (ALT, AST and GGT) at baseline, revealed solid predictability for MASLD in a combined panel (AUC = 0.8), and lastly demonstrated the highest accuracy in identifying individuals with high liver fat among all individuals with obesity. Finally, several MASLD- and hepatocellular carcinoma-related miRNAs decreased significantly following weight loss and liver fat reduction in the MASLD group.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle-Based miRNA Profiling in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Secondary Analysis of the MULTISITE Clinical Trial","authors":"Katja Lund Cliff,&nbsp;Dominic Guanzon,&nbsp;Andrew Lai,&nbsp;Katherin Scholz-Romero,&nbsp;Gunna Christiansen,&nbsp;Aase Handberg,&nbsp;Carlos Salomon,&nbsp;Maiken Mellergaard","doi":"10.1002/jex2.70173","DOIUrl":"https://doi.org/10.1002/jex2.70173","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the worldwide leading cause of liver-related mortality with a prevalence of 75% among individuals with obesity and lacking screenings tools. Extracellular vesicles (EVs)-based microRNAs (miRNAs) have emerged as promising biomarkers with important roles in the pathogenesis of MASLD. This study aimed to characterize EV-based miRNA profiles in individuals with obesity and MASLD before and during weight loss intervention. Small RNA sequencing was used to profile EV-miRNAs from plasma across three groups: individuals with obesity and MASLD (<i>n</i> = 35), individuals with obesity without hepatic steatosis (<i>n</i> = 24) and lean controls without hepatic steatosis (<i>n</i> = 26). Further, the MASLD group underwent a personalized weight-loss intervention. The liver and MASLD-related miR-122-5p and three other miRNAs were differentially expressed in the MASLD group compared with the obesity control group at baseline. Moreover, miR-122-5p correlated with liver fat and liver enzymes (ALT, AST and GGT) at baseline, revealed solid predictability for MASLD in a combined panel (AUC = 0.8), and lastly demonstrated the highest accuracy in identifying individuals with high liver fat among all individuals with obesity. Finally, several MASLD- and hepatocellular carcinoma-related miRNAs decreased significantly following weight loss and liver fat reduction in the MASLD group.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered MicroRNA Signatures in Circulating Extracellular Vesicles Reflect Aortic Dilation in Takayasu Arteritis","authors":"Kohei Kawajiri,&nbsp;Shun Nakagama,&nbsp;Tetsuo Sasano,&nbsp;Yasuhiro Maejima","doi":"10.1002/jex2.70179","DOIUrl":"https://doi.org/10.1002/jex2.70179","url":null,"abstract":"<p>Takayasu arteritis (TAK) is a large-vessel vasculitis that can lead to aneurysmal dilation, yet reliable circulating biomarkers for vascular remodelling remain lacking. Extracellular vesicles (EVs) carry miRNAs implicated in vascular biology, but their relevance to TAK has not been fully explored.</p><p>Circulating EVs were isolated from serum of 54 patients with TAK and healthy controls (HC), characterized, and profiled for miRNA content. Effects on endothelial cells (ECs) and monocytes were examined in vitro, and the diagnostic performance of EV-associated miR-223-3p for aortic dilation was assessed by ROC analysis.</p><p>Circulating EVs from patients with TAK exhibited a distinct miRNA profile compared with HC. HC-EVs reduced the transcript abundance of <i>ICAM-1</i> and <i>VCAM-1</i> in ECs, an effect attenuated in TAK-EVs and accompanied by enhanced monocyte adhesion. EV-derived miR-223-3p was upregulated in TAK but selectively downregulated in patients with aortic dilation. EV-associated miR-223-3p discriminated aortic dilation with an AUC of 0.748, exceeding that of CRP and ESR. Flow cytometric profiling revealed a reduction in platelet-derived EVs in patients with aortic dilation.</p><p>Reduced EV-associated miR-223-3p is associated with aortic dilation in TAK and may serve as a candidate biomarker as an adjunct to imaging-based assessment, warranting prospective validation in larger cohorts.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148783510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered MicroRNA Signatures in Circulating Extracellular Vesicles Reflect Aortic Dilation in Takayasu Arteritis","authors":"Kohei Kawajiri,&nbsp;Shun Nakagama,&nbsp;Tetsuo Sasano,&nbsp;Yasuhiro Maejima","doi":"10.1002/jex2.70179","DOIUrl":"https://doi.org/10.1002/jex2.70179","url":null,"abstract":"<p>Takayasu arteritis (TAK) is a large-vessel vasculitis that can lead to aneurysmal dilation, yet reliable circulating biomarkers for vascular remodelling remain lacking. Extracellular vesicles (EVs) carry miRNAs implicated in vascular biology, but their relevance to TAK has not been fully explored.</p><p>Circulating EVs were isolated from serum of 54 patients with TAK and healthy controls (HC), characterized, and profiled for miRNA content. Effects on endothelial cells (ECs) and monocytes were examined in vitro, and the diagnostic performance of EV-associated miR-223-3p for aortic dilation was assessed by ROC analysis.</p><p>Circulating EVs from patients with TAK exhibited a distinct miRNA profile compared with HC. HC-EVs reduced the transcript abundance of <i>ICAM-1</i> and <i>VCAM-1</i> in ECs, an effect attenuated in TAK-EVs and accompanied by enhanced monocyte adhesion. EV-derived miR-223-3p was upregulated in TAK but selectively downregulated in patients with aortic dilation. EV-associated miR-223-3p discriminated aortic dilation with an AUC of 0.748, exceeding that of CRP and ESR. Flow cytometric profiling revealed a reduction in platelet-derived EVs in patients with aortic dilation.</p><p>Reduced EV-associated miR-223-3p is associated with aortic dilation in TAK and may serve as a candidate biomarker as an adjunct to imaging-based assessment, warranting prospective validation in larger cohorts.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"5 8","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70179","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}