Journal of Extracellular Vesicles最新文献

{"title":"Shear-Activated von Willebrand Factor Captures Extracellular Vesicles to Promote Platelet Activation and Metastasis","authors":"Yuanyuan Wang,&nbsp;Xiaobo Liu,&nbsp;Pascal Nakielski,&nbsp;Katrin Nekipelov,&nbsp;Amanda Salviano-Silva,&nbsp;Alper Topuz,&nbsp;Alexander T. Bauer,&nbsp;Julian Kött,&nbsp;Jannis Akrivakis,&nbsp;Santra Brenna,&nbsp;Tomasz Downar,&nbsp;Neus Feliu,&nbsp;Gerd Bendas,&nbsp;Berta Puig,&nbsp;Stefan W. Schneider,&nbsp;Dmitry A. Fedosov,&nbsp;Christian Gorzelanny","doi":"10.1002/jev2.70349","DOIUrl":"10.1002/jev2.70349","url":null,"abstract":"<p>Plasma proteins are increasingly recognized as key regulators of extracellular vesicle (EV) behaviour in circulation. However, von Willebrand factor (vWF)—the largest multimeric glycoprotein in blood and the only blood protein activated by shear—has received little attention in this context. Under elevated shear stress, vWF transitions from a compact globular form to an extended adhesive conformation. Although elevated plasma vWF levels are associated with hypercoagulation in conditions such as malaria, COVID-19, and cancer, its interactions with EVs or cells under physiological flow have not been systematically investigated. Here, we show that shear-activated vWF functions as a size-selective molecular filter that preferentially captures objects smaller than ∼4 µm, including platelets and tumour-derived EVs, while excluding larger cells. Although intact tumour cells do not directly bind vWF under physiological flow, the coordinated binding of EVs and platelets to extended vWF promotes platelet aggregation, which subsequently traps circulating tumour cells and fosters metastatic dissemination. Our findings reveal a previously unrecognized role of vWF as a shear-dependent EV-binding protein that brings EVs and platelets together to enhance coagulation and metastasis. These EV–vWF–platelet aggregates may represent promising biomarkers or therapeutic targets for the prevention of hypercoagulation in cancer and other thrombo-inflammatory diseases.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rituximab Binding Endows CD20+ Extracellular Vesicles With NK Cell-Activating Properties in B Cell Lymphoma","authors":"Adrián V. Otero,&nbsp;Paula Soledad Pérez,&nbsp;Belen Gaete-Ramírez,&nbsp;Gregorio Cordini,&nbsp;Matías Norte,&nbsp;Enriqueta Martínez,&nbsp;Nicolás Marsol,&nbsp;Cecilia Malusardi,&nbsp;Sofía Rivarola,&nbsp;Ana Cantillo,&nbsp;María Luz Leicaj,&nbsp;Constanza Russo,&nbsp;Juan Quarroz Braghini,&nbsp;Federico Penas,&nbsp;Glenda Ernst,&nbsp;Cecilia Cabral,&nbsp;Silvina Palmer,&nbsp;Manuel Varas-Godoy,&nbsp;Lourdes Arruvito,&nbsp;Matías Ostrowski","doi":"10.1002/jev2.70352","DOIUrl":"10.1002/jev2.70352","url":null,"abstract":"<p>Non-Hodgkin lymphoma (NHL), predominantly B cell lymphomas (B-NHL), is currently treated with chemotherapy combined with rituximab (RTX), an anti-CD20 monoclonal antibody. Despite substantial therapeutic advances, treatment resistance and disease relapse continue to affect a significant fraction of patients. The mechanisms by which the tumour microenvironment and other factors influence RTX efficacy are not fully elucidated. Herein, we hypothesized that CD20+ extracellular vesicles (EVs) shed by B cell lymphomas are recognized by RTX forming immune complexes that modulate natural killer (NK) cell activity via Fcγ receptor (FcγR) interactions. EVs isolated from lymph node explants and plasma samples of B-NHL patients contained abundant CD20+ vesicles, which were particularly enriched in advanced disease. RTX specifically bound CD20 on these EVs, generating EV-RTX immune complexes. Functional studies employing EVs from a B-NHL cell line and from patient-derived samples demonstrated that, whereas EVs suppressed NK cell activation and cytotoxicity, EV-RTX immune complexes reversed this inhibitory effect and enhanced NK cell effector functions. Indeed, EV-RTX immune complexes specifically triggered FcγRIIIa-dependent NK cell activation, evidenced by increased Syk phosphorylation, CD69 expression, and enhanced lytic activity against target cells. Our findings uncover a previously unrecognized mechanism by which RTX, through the formation of immune complexes with CD20+ EVs, promotes NK cell activation and may enhance therapeutic efficacy. More broadly, these results demonstrate that antibody binding can endow EVs with novel immunomodulatory properties, revealing a potential mechanism by which therapeutic antibodies reshape EV function and influence anti-tumour immunity.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphatic Drainage of Cerebrospinal Fluid Using Lymph Node Seeker 64Cu-Labeled Gram-Negative Bacterial Extracellular Vesicles With Positron Emission Tomography (PET)","authors":"Kyuwan Kim,&nbsp;Changjin Lee,&nbsp;Hayoung Shin,&nbsp;Ran Ji Yoo,&nbsp;Yoori Choi,&nbsp;Chanwoo Lee,&nbsp;Insoo Kim,&nbsp;Jaewook Lee,&nbsp;Minseok Suh,&nbsp;Yun-Sang Lee,&nbsp;Yong Song Gho,&nbsp;Dong Soo Lee","doi":"10.1002/jev2.70347","DOIUrl":"10.1002/jev2.70347","url":null,"abstract":"<p>Cerebrospinal fluid (CSF) is drained into the systemic lymphatics via paravertebral lymph nodes. Superficial and deep cervical lymph nodes collect CSF in mice, but the exact and quantified routes are unknown. Recently, we simultaneously visualized cervical, sacral and iliac lymph nodes via serial imaging on the intrathecal [⁶⁴Cu]Cu-albumin positron emission tomography. Paravertebral lymph nodes might act as sentinels to monitor the CSF, brain, and spinal cord. We used ⁶⁴Cu-labeled <i>Escherichia coli</i> extracellular vesicles, outer membrane vesicles (OMVs), as lymph node seekers for intrathecal administration and quantified the differential amounts of various paravertebral lymph nodes along the axis of the brain and spinal cord in mice. The quantified results revealed 77.3% in superficial and deep cervical lymph nodes, 11.4% in abdominal/pelvic lymph nodes and 11.3% in sacral lymph nodes. Click-labeled [⁶⁴Cu]Cu-OMVs were drained to reach and stop at the lymph nodes on serial quantification. The cervical lymph nodes drained most of the OMV-laden CSF, which is proportional to the surface areas of the brain (70%) and spinal cord in mice. We propose that all paravertebral lymph nodes monitor the segmental regions of the brain and spinal cord as immediate sentinel lymph nodes against the central nervous system.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron Salts, but Not Iron Oxide Nanoparticles, Drive High-Yield Production of Iron-Engineered Extracellular Vesicles","authors":"Elliot Thouvenot,&nbsp;Aurore Van de Walle,&nbsp;Jean-Michel Guigner,&nbsp;Ali Abou-Hassan,&nbsp;Lorena Martin-Jaular,&nbsp;Amanda K. A. Silva,&nbsp;Claire Wilhelm","doi":"10.1002/jev2.70346","DOIUrl":"10.1002/jev2.70346","url":null,"abstract":"<p>Efficient production of iron-engineered extracellular vesicles (EVs) is of interest for their use as delivery systems in biotherapy. In this study, we investigated the role of iron in EV biogenesis and evaluated a scalable fluidic strategy for their mass production using turbulence stimulation in bioreactors. Murine mesenchymal stem cells were loaded with iron via ferric quinate or iron oxide nanoparticles (IONPs) and subsequently subjected to turbulence stimulation or serum starvation to induce EV secretion. Using elemental spectroscopy and cryogenic electron microscopy, we found that prolonged incubation with ferric quinate combined with turbulence stimulation resulted in the highest EV yield—60,000 EVs per cell in 3 h—and enabled efficient iron transfer from cells to EVs. In contrast, IONP treatment did not increase EV yield compared to control and showed high variability in iron transfer, as probed by EV magnetophoretic mobility. TEM and XEDS analyses confirmed ferritin-bound iron encapsulation within EVs, whereas IONPs were poorly internalised. These results highlight the promising role of ionic iron in EV formation and content, demonstrating how iron source, concentration, and incubation duration influence both EV biogenesis and iron engineering.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'Endothelial Integrin-Linked Kinase (ILK) Deficiency Promotes Endothelial Activation and Cardiovascular Dysfunction via Receptor Interacting Protein Kinase-1 (RIPK1) Enriched-Extracellular Vesicle Signalling'","authors":"","doi":"10.1002/jev2.70344","DOIUrl":"10.1002/jev2.70344","url":null,"abstract":"<p>Cook-Calvete, A., M. Delgado-Marín, S. Jorquera Ortega, et al. 2026. “Endothelial Integrin-Linked Kinase (ILK) Deficiency Promotes Endothelial Activation and Cardiovascular Dysfunction via Receptor Interacting Protein Kinase-1 (RIPK1) Enriched-Extracellular Vesicle Signalling.” <i>Journal of Extracellular Vesicles</i> 15, no. 6: e70335. https://doi.org/10.1002/jev2.70335</p><p>In the originally published article, author Blanca Fernandez-Rodriguez's name was given incorrectly as Blanca Rodríguez-Fernandez. Additionally, Figure 6 was inadvertently published twice as Figure 6 and Figure 7. The correct Figure 7 is shown below. The online version of the article has been updated.</p><p>We apologize for this error.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils Promote Metabolic Dysfunction-Associated Steatotic Liver Disease Through Extracellular Vesicle-mediated Lipid Transfer","authors":"Sanjeeb Shrestha,&nbsp;Soo-Jung Jung,&nbsp;Seong-Min Lim,&nbsp;Yu-Bin Lee,&nbsp;Hyeung-Wook Shin,&nbsp;Hoyul Lee,&nbsp;Hee-Kyung Jin,&nbsp;Jae-Sung Bae,&nbsp;Jae-Han Jeon,&nbsp;Lai Guan Ng,&nbsp;Chang-Won Hong","doi":"10.1002/jev2.70350","DOIUrl":"https://doi.org/10.1002/jev2.70350","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis are leading causes of chronic liver disease, yet the contribution of neutrophils to early hepatocellular lipid accumulation remains poorly understood. Here, we investigated the role of neutrophils in hepatic lipid deposition during early MASLD development. Neutrophils acquired extracellular fatty acids (FAs) via FATP2 and CD36 and stored them as triglycerides (TGs). These lipid-laden neutrophils (LNs) did not utilize FAs for energy production or lipid mediator synthesis but instead transferred lipid cargo to hepatocytes through extracellular vesicles (EVs). Neutrophil-derived EVs were enriched with TGs and lipid metabolism-regulating microRNAs, augmenting TG accumulation in hepatocytes. Peripheral neutrophils isolated from high-fat diet-fed mice exhibited a lipid-laden phenotype, and adoptive transfer of LNs and EVs derived from LNs increased hepatic fat accumulation in recipient mice. In patients with MASLD, circulating neutrophils showed lipid droplet accumulation with increased TGs and enrichment of lipid-associated miRNAs while plasma EVs were also enriched with TGs and lipid-associated miRNAs. Single-cell RNA sequencing of peripheral immune cells identified a neutrophil subpopulation characterized by enhanced lipid-handling and EV-related gene expression. These findings identify neutrophil-mediated lipid transfer via EVs as a mechanistic link between innate immune activation and hepatic lipid accumulation during early MASLD.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils Promote Metabolic Dysfunction-Associated Steatotic Liver Disease Through Extracellular Vesicle-mediated Lipid Transfer","authors":"Sanjeeb Shrestha,&nbsp;Soo-Jung Jung,&nbsp;Seong-Min Lim,&nbsp;Yu-Bin Lee,&nbsp;Hyeung-Wook Shin,&nbsp;Hoyul Lee,&nbsp;Hee-Kyung Jin,&nbsp;Jae-Sung Bae,&nbsp;Jae-Han Jeon,&nbsp;Lai Guan Ng,&nbsp;Chang-Won Hong","doi":"10.1002/jev2.70350","DOIUrl":"https://doi.org/10.1002/jev2.70350","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis are leading causes of chronic liver disease, yet the contribution of neutrophils to early hepatocellular lipid accumulation remains poorly understood. Here, we investigated the role of neutrophils in hepatic lipid deposition during early MASLD development. Neutrophils acquired extracellular fatty acids (FAs) via FATP2 and CD36 and stored them as triglycerides (TGs). These lipid-laden neutrophils (LNs) did not utilize FAs for energy production or lipid mediator synthesis but instead transferred lipid cargo to hepatocytes through extracellular vesicles (EVs). Neutrophil-derived EVs were enriched with TGs and lipid metabolism-regulating microRNAs, augmenting TG accumulation in hepatocytes. Peripheral neutrophils isolated from high-fat diet-fed mice exhibited a lipid-laden phenotype, and adoptive transfer of LNs and EVs derived from LNs increased hepatic fat accumulation in recipient mice. In patients with MASLD, circulating neutrophils showed lipid droplet accumulation with increased TGs and enrichment of lipid-associated miRNAs while plasma EVs were also enriched with TGs and lipid-associated miRNAs. Single-cell RNA sequencing of peripheral immune cells identified a neutrophil subpopulation characterized by enhanced lipid-handling and EV-related gene expression. These findings identify neutrophil-mediated lipid transfer via EVs as a mechanistic link between innate immune activation and hepatic lipid accumulation during early MASLD.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 8","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota-Derived Bacterial Extracellular Vesicles in COVID-19: Their Signature and Immunological Impact","authors":"Aya Ishizaka,&nbsp;Michiko Koga,&nbsp;Tomoya Hayashi,&nbsp;Ken J Ishii,&nbsp;Hiroyuki Yamamoto,&nbsp;Hiroshi Yotsuyanagi,&nbsp;Taketoshi Mizutani","doi":"10.1002/jev2.70341","DOIUrl":"10.1002/jev2.70341","url":null,"abstract":"<p>Gut microbial dysbiosis has been observed in several diseases. Although causal links and direct effects on host cells remain unclear, bacteria-derived extracellular vesicles (BEVs) from the gut microbiota may regulate the host immune response. We examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the gut microbiome and BEVs release, and the effects of released BEVs on cytokine responses in monocyte-derived cell lines. Fecal samples from 17 patients with coronavirus disease 2019 (COVID-19) and 20 healthy individuals were collected to isolate bacterial and BEV fractions. Parental BEV-releasing bacteria were identified from vesicle-encapsulated bacterial DNA by 16S rRNA gene sequencing. Patients with COVID-19 exhibited altered gut microbiota composition and the profile of bacterial DNA-containing BEVs (dcBEVs) release compared to healthy controls. BEVs from patients, but not from healthy individuals, significantly changed cytokine levels in U937 monocyte cells. Following COVID-19 recovery, dcBEV profiles diverged into two distinct groups: those that retained the capacity to induce cytokines in monocytes and those that lost this functionality. BEVs from single bacterial cultures within families altered after COVID-19 onset affected the expression of genes in monocytes, primarily immune-response genes, notably chemokine ligands and G protein-coupled receptors. SARS-CoV-2–induced dysbiosis alters the profile of dcBEVs release, thereby modulating the host immune response and potentially contributing to COVID-19 pathogenesis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S100A9 Aggravates Cardiac Fibrosis by TLR4/PGC-1α Mediated Macrophage-Myofibroblast Crosstalk","authors":"Yiting Zhao,&nbsp;Yaqin Zhang,&nbsp;Qiang Yuan,&nbsp;XiaoFeng Fang,&nbsp;Jianlong Sheng,&nbsp;Yuhang Deng,&nbsp;Shichun Shen","doi":"10.1002/jev2.70338","DOIUrl":"10.1002/jev2.70338","url":null,"abstract":"<p>Fibrosis is a critical component of ventricular remodelling after myocardial ischemia, and the activation and expansion of cardiac fibroblasts represent key drivers of this process. Our previous work identified S100A9-dependent macrophage-to-myofibroblast transition (MMT) as a newly recognized source of myofibroblasts in the post-MIR heart. However, the mechanisms by which S100A9 regulates MMT remain incompletely understood. Here, using multiple genetically engineered mouse models, MIR and MI model, and in vitro multicellular co-culture systems, we investigated the role of S100A9 in regulating fibroblast-derived migrasome release during MMT. We found that macrophage-derived S100A9 promotes mitochondrial dysfunction and migrasome release in cardiac fibroblasts through TLR4/PGC1α signalling following MIR. These fibroblast-derived migrasomes, in turn, activate integrin/Src signalling in macrophages, triggering MMT and accelerating cardiac fibrosis. Importantly, we delineate how macrophage-derived S100A9 orchestrates crosstalk between fibroblasts and immune cells and identify migrasome-mediated activation of MMT as a previously unrecognized mechanism driving post-MIR fibrotic remodelling. Our findings suggest that targeting S100A9-induced migrasome release and downstream MMT signalling may represent a promising therapeutic strategy to mitigate pathological cardiac fibrosis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic Acid B Upregulates miR-744-5p Expression in Peripheral Blood Mononuclear Cell–Derived Extracellular Vesicles to Alleviate Uremic Cardiomyopathy","authors":"Ziran Wang,&nbsp;Jiaojiao Hao,&nbsp;Yaxi Shang,&nbsp;Wenli Ma,&nbsp;Nan Wang,&nbsp;Weidong Wang,&nbsp;Qingzhu Tang,&nbsp;Xiangning Du,&nbsp;Fan Yang,&nbsp;Biaojie Qin,&nbsp;Shuni Chen,&nbsp;Kun Xiao,&nbsp;Longkai Li,&nbsp;Xianan Guo,&nbsp;Xin Qi,&nbsp;Shuang Meng,&nbsp;Huiyi Song,&nbsp;Hongli Lin","doi":"10.1002/jev2.70331","DOIUrl":"https://doi.org/10.1002/jev2.70331","url":null,"abstract":"<p>Uremic cardiomyopathy (UCM) is a severe complication of uraemia that lacks effective treatments. The role of immune dysfunction in haemodialysis patients with UCM remains unclear. Peripheral blood mononuclear cells (PBMCs) are major components of the immune system; however, they do not directly contact cardiomyocytes. In general, extracellular vesicles (EVs) function as intercellular communication mediators. Therefore, in this study, we first investigated the role of PBMC-derived EVs (PBMC-EVs) in UCM and identified EV-miR-744-5p as a key molecule involved in PBMC–cardiomyocyte communication. Mechanistically, indoxyl sulphate (IS) downregulated miR-744-5p expression in PBMC-EVs, leading to IGF2R upregulation in cardiomyocytes, thereby exacerbating myocardial injury via induction of hypertrophy, apoptosis and inflammatory pathway activation in the cardiomyocytes. We also explored the potential of natural products to treat UCM by modifying PBMC-EVs and found that the traditional Chinese medicine monomer salvianolic acid B (Sal B) could bind to YY1, enhancing miR-744-5p expression in PBMC-EVs and thus mitigating myocardial injury in UCM. Taken together, these findings indicate the critical role of PBMC-EVs in UCM and suggest the cardioprotective effects of Sal B via PBMC-EV modification. They also provide novel insights into immune mechanisms underlying UCM, particularly indicating that targeting PBMC-EVs may be a promising UCM treatment strategy.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 7","pages":""},"PeriodicalIF":21.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148467526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}