Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Integrated Single-Cell Atlas Reveals Cross-Subtype Heterogeneity in Human Pulmonary Hypertension.","authors":"Huazhuo Feng, Jiaxuan Lai, Xuqi Yang, Xudong Cui, Shaocong Mo, Yazhi Feng, Qiang Chen, Bihua Zhong, Wenju Lu, Yuqin Chen, Kai Yang, Jian Wang","doi":"10.1161/ATVBAHA.126.324594","DOIUrl":"10.1161/ATVBAHA.126.324594","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a severe vascular disorder characterized by pathological pulmonary vascular remodeling. Although single-cell RNA sequencing has provided insights into PH, patient studies remain fragmented across clinical subtypes and are processed with heterogeneous pipelines, limiting cross-study comparability and integrative interpretation of disease-relevant cellular states in human PH.</p><p><strong>Methods: </strong>We integrated single-cell RNA sequencing data sets to construct a core PH-specific cellular atlas using a standardized quantification and batch-correction pipeline, followed by hierarchical cell type annotation to define major lineages and finer cell states. We then performed comparative analyses to reassess reported cellular alterations within a unified reference. Building on this atlas, we developed PH-Map, a multitask learning tool pretrained on this atlas for rapid hierarchical cell annotation and validated it in independent external cohorts.</p><p><strong>Results: </strong>The core PH-specific atlas comprises 235 621 high-quality cells from 64 human samples spanning idiopathic pulmonary arterial hypertension, systemic sclerosis-associated pulmonary arterial hypertension, chronic thromboembolic PH, and healthy controls, organized into 6 major lineages and 58 distinct cell states. Cross-subtype comparison revealed shared and subtype-specific remodeling across vascular and immune compartments, including redefined smooth muscle cell states, fibroblast-associated complement activation in idiopathic pulmonary arterial hypertension, and heterogeneous immune transcriptional programs. We additionally observed system-dependent differences, including variable major histocompatibility complex class II activation in capillary endothelial cells across animal models versus human PH and convergent phenotypic shifts in primary cultured endothelial cells relative to native lung endothelial cells. PH-Map showed stable hierarchical annotation performance in external cohorts across multiple levels of annotation granularity with improved computational efficiency.</p><p><strong>Conclusions: </strong>This core human single-cell PH atlas enables systematic cross-subtype comparison and delineates shared and subtype-specific cellular programs across vascular and immune compartments. Together with PH-Map, it supports reproducible hierarchical annotation and prioritization of candidate cell states and pathways for downstream studies.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324594"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Spatial Transcriptomics Reveals Sex-Specific Differences Driving Carotid Atherosclerotic Plaque Instability.","authors":"Jae Hyun Byun, Helena Papacostas Quintanilla, Karina Gasbarrino, Ioanna Gianopoulos, Ashot S Harutyunyan, Spyros Oikonomopoulos, John P Veinot, Huaien Zheng, Jiannis Ragoussis, Stella S Daskalopoulou","doi":"10.1161/ATVBAHA.125.323505","DOIUrl":"10.1161/ATVBAHA.125.323505","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke remains a leading contributor to cardiovascular disease, and unstable atherosclerotic plaques in the carotid arteries are an important contributor to its pathogenesis. Notably, sex differences exist in plaque composition and morphology; whereas males are more likely to develop unstable plaques, females present with worse outcomes poststroke. As such, this study aims to elucidate sex-specific cellular and molecular mechanisms driving carotid plaque instability.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on carotid endarterectomy specimens from male and female patients with stable or unstable plaques, profiling over 64 000 cells. To spatially contextualize these findings, we integrated single-cell RNA sequencing data with CosMx high-plex spatial transcriptomics using the human discovery 6k RNA panel to map gene expression and cell type localization within key histological regions defining instability.</p><p><strong>Results: </strong>Single-cell RNA sequencing revealed that vascular smooth muscle cells (VSMCs), T lymphocytes, and macrophages comprised ≈88% of plaque-resident cells, with distinct sex-specific differences in relation to instability. In males, unstable plaques showed depletion of contractile VSMCs and an abundance of inflammatory synthetic and macrophage-like VSMCs, alongside increased inflammatory macrophages and activated naive T lymphocytes. In contrast, female unstable plaques retained relatively more contractile VSMCs but exhibited greater expansion of cytotoxic T lymphocytes and foam-cell macrophages. Sex-specific cell-cell interaction analysis demonstrated increased VSMC-to-stromal interactions and elevated macrophage-macrophage signaling in male and female unstable plaques, respectively. Through spatial transcriptomics, inflammatory synthetic VSMCs identified by single-cell RNA sequencing dominated the lipid core in both male and female unstable plaques. However, only in males did these cells also replace the fibrotic cap, forming immune-rich niches among themselves and with macrophage-like VSMCs.</p><p><strong>Conclusions: </strong>Overall, these findings uncover distinct cellular and spatial mechanisms driving plaque destabilization in males and females, highlighting the need for sex-specific approaches to the diagnosis and treatment of carotid atherosclerosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323505"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophils Exhibit Delayed Spontaneous Apoptosis and Resistance to Regulatory T-Cell-Induced Apoptosis in Patients With Chronic Coronary Syndrome-Brief Report.","authors":"Maike Schneider, Camilla Skoglund, Rosanna W S Chung, Lena Jonasson","doi":"10.1161/ATVBAHA.126.324652","DOIUrl":"10.1161/ATVBAHA.126.324652","url":null,"abstract":"<p><strong>Background: </strong>Persistent inflammation is linked to poor outcomes in patients with a history of myocardial infarction. The inflammatory state has been associated with activation of neutrophils as well as with regulatory T-cell (T_reg) deficiency. The role of T_regs in the regulation of neutrophil survival has been postulated recently. Here, we investigated neutrophil apoptosis along with the potential impact of T_regs on neutrophil apoptosis in patients with postmyocardial infarction chronic coronary syndrome, compared with healthy controls.</p><p><strong>Methods: </strong>Twenty patients and 19 controls were included. Neutrophil apoptosis was assessed after 5-hour culture with or without IL (interleukin)-10, TNF (tumor necrosis factor), or lipopolysaccharide. Neutrophil phenotype was evaluated through flow cytometry analysis of surface receptors (CD66b [cluster of differentiation] and CXCR4 [C-X-C chemokine receptor type 4]) and ex vivo release of cytokines and proteins. The ability of T_regs to induce neutrophil apoptosis was examined in autologous neutrophil-T_reg cocultures.</p><p><strong>Results: </strong>Spontaneous neutrophil apoptosis was significantly delayed in patients compared with controls (10.3% versus 19.2%, <i>P</i>=0.025). Also, neutrophils from patients overexpressed CD66b and CXCR4 and were more prone to release proinflammatory mediators. Notably, T_regs induced neutrophil apoptosis in healthy subjects, but not in patients, indicating a loss of T_reg-mediated regulation in the latter. There was no evidence that IL-10 had any influence on neutrophil apoptosis. However, cell-to-cell contact was found essential for T_reg-induced neutrophil apoptosis.</p><p><strong>Conclusions: </strong>Patients with postmyocardial infarction chronic coronary syndrome display delayed neutrophil apoptosis and a proinflammatory neutrophil phenotype that is resistant to T_reg-mediated apoptosis. Neutrophil dysfunction may contribute to persistent inflammation in patients with postmyocardial infarction chronic coronary syndrome, and as such constitutes a novel therapeutic target.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324652"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloid Cell-Specific Deletion of LGR4 Suppresses Atherosclerotic Lesion Formation.","authors":"Ishita Kathuria, Ravi Varma Aithabathula, Md Abdullah Al Mamun, Naveed Pervaiz, Indira Neeli, Malvin Ofosu-Boateng, Udai P Singh, Srija Rairao, Maxwell A Gyamfi, Ki-Suk Kim, Bhupesh Singla","doi":"10.1161/ATVBAHA.125.324159","DOIUrl":"10.1161/ATVBAHA.125.324159","url":null,"abstract":"<p><strong>Background: </strong>Monocyte-derived macrophages play a significant role in the initiation and progression of atherosclerosis by transforming into lipid-laden foam cells and regulating vascular inflammation. However, the molecular mechanisms that regulate macrophage lipid accumulation, phenotype, efferocytic capacity, and atherosclerosis are incompletely understood. Our preliminary studies revealed increased expression of LGR4 (leucine-rich repeat-containing G protein-coupled receptor 4) in human atherosclerotic arteries. Additional experiments demonstrated increased LGR4 levels in atherogenic oxidized low-density lipoprotein-treated macrophages. However, the macrophage-specific role of LGR4 in atherogenesis has never been investigated.</p><p><strong>Methods: </strong>To investigate the role of myeloid cell Lgr4 in atherosclerosis development, myeloid cell-specific <i>Lgr4</i> knockout (<i>Lgr4</i>^f/f <i>LysM</i> Cre^+/-, <i>Lgr4</i>^ΔM) and littermate control <i>Lgr4</i>^f/f (<i>Lgr4</i>^WT) mice were injected intraperitoneally with adeno-associated viral vector (serotype 8) for h<i>PCSK9</i> and fed a Western diet for 16 weeks. Various in vitro cell-based assays, molecular biology techniques, and immunohistological approaches were used to evaluate the functional roles of macrophage Lgr4 and underlying signaling mechanisms.</p><p><strong>Results: </strong>Oil red O staining of whole aortas and aortic root sections demonstrated reduced atherosclerosis in <i>Lgr4</i>^ΔM mice compared with sex-matched <i>Lgr4</i>^WT mice. However, no changes in circulating monocyte frequencies were detected. Histochemical staining performed on aortic root sections revealed smaller necrotic cores and higher collagen content in <i>Lgr4</i>^ΔM mice. Additionally, <i>Lgr4</i>^ΔM mice exhibited lower fat mass and blood glucose levels, while plasma total cholesterol was comparable to that of control mice. Further in vitro and ex vivo studies demonstrated reduced lipid accumulation, enhanced efferocytic capacity, a suppressed proinflammatory phenotype, and attenuated expression of different low-density lipoprotein uptake genes in <i>Lgr4</i>-deficient macrophages. Moreover, <i>Lgr4</i> knockout macrophages displayed increased cholesterol efflux capacity and reduced activation of oxidized low-density lipoprotein-induced Wnt (Wingless-related integration site)/β-catenin signaling.</p><p><strong>Conclusions: </strong>These findings suggest that myeloid cell <i>Lgr4</i> contributes to atherosclerotic lesion formation via stimulating macrophage lipid accumulation, impairing efferocytic capacity, and promoting a proinflammatory phenotype. Collectively, these results identify macrophage LGR4 as a novel therapeutic target for atherosclerosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324159"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13336305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366786","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":"Hyperadhesive von Willebrand Factor Contributes to Pathogenesis of Preeclampsia.","authors":"Yajuan Wang, Chenyu Wang, Katie L Houck, Xiaoli Gao, Yuanyuan Chen, Xin Xu, Xue Zhao, Miguel A Cruz, Shu Zhang, Chester Q Li, Fengxia Xue, Min Li, Swati Shree, Jing-Fei Dong, Cha Han","doi":"10.1161/ATVBAHA.125.324258","DOIUrl":"10.1161/ATVBAHA.125.324258","url":null,"abstract":"<p><strong>Background: </strong>Preeclampsia is the most common complication of pregnancy, significantly affecting maternal and fetal health, and is characterized by placental and systemic endotheliopathy. Patients with preeclampsia have elevated levels of VWF (von Willebrand Factor), which is associated with poor clinical outcomes. However, whether VWF serves as a marker for endotheliopathy or contributes to the pathogenesis of preeclampsia remains poorly understood.</p><p><strong>Methods: </strong>We investigated the role of hyperadhesive VWF in the development of preeclampsia by studying patients, evaluating mouse models, and performing in vitro experiments.</p><p><strong>Results: </strong>We show that patients develop VWF- and fibrin-rich thrombosis in the placenta and have significantly elevated levels of VWF adhesive activity and placenta-derived extracellular vesicles. In mouse models, pregnant wild-type mice infused with hyperadhesive VWF alone, or in combination with placenta-derived extracellular vesicles, developed a preeclampsia-like condition, which was reduced by the VWF-cleaving metalloprotease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13). Furthermore, <i>ADAMTS13</i>-deficient mice with high baseline VWF (<i>ADAMTS13</i>^<i>-/</i>^{<i>-/casa</i>}) developed a preeclampsia-like condition spontaneously, with VWF adhesive activity increasing 5.6-fold and placenta-derived extracellular vesicles increasing 2.9-fold during late pregnancy. VWF became hyperadhesive during pregnancy by undergoing conformational changes and promoted preeclampsia-associated endotheliopathy by enhancing the interaction of placenta-derived extracellular vesicles with endothelial cells.</p><p><strong>Conclusions: </strong>This study demonstrates that hyperadhesive VWF plays a causal role in preeclampsia and is a potential therapeutic target.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324258"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148216147","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":"Interpreting Pulmonary Hypertension Beyond Single Cells.","authors":"Jinjiang Pang, Shengyu Li, Guangyu Wang, Jun-Ichi Abe","doi":"10.1161/ATVBAHA.126.324960","DOIUrl":"10.1161/ATVBAHA.126.324960","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324960"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315356","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":"Endothelial Nucleoporin93 (Nup93) Maintains Vascular Homeostasis via Sun1-Dependent Regulation of RhoA/ROCK Activity.","authors":"Tung D Nguyen, Miles D Eckrich, Yumna Z Khan, Faruk Hossen, Riya Makim, Hannah A Durr, Julia Michalkiewicz, Mihir K Rao, Justin M Banks, Amy X Ren, Michael A Winek, Luis Henrique O de Moraes, James C Lee, Shane A Phillips, Monica Y Lee","doi":"10.1161/ATVBAHA.126.324964","DOIUrl":"10.1161/ATVBAHA.126.324964","url":null,"abstract":"<p><strong>Background: </strong>As the innermost lining of blood vessels, endothelial cells regulate barrier function, maintain vascular tone, and limit inflammation for vessel health. Involved in various fundamental endothelial processes, RhoA (Ras homolog family member A)/ROCK (Rho-associated coiled-coil containing protein kinase) signaling has been identified as a major contributor to age-associated hypertension and vascular disease; RhoA/ROCK hyperactivation promotes vessel permeability and impairs nitric oxide (NO) production. Recent studies identify Sun1 (Sad1 and UNC84 [protein UNC-84 homolog A] domain-containing protein 1), a key component of the linker of nucleoskeleton and cytoskeleton complex, as a major repressor of RhoA/ROCK activity. Our latest studies identify endothelial loss of Nup93 (nucleoporin93), a component of the nuclear pore complex, as a hallmark of vascular aging. Insinuating a role for nuclear envelope components in vessel homeostasis, the role of Nup93 in RhoA/ROCK signal regulation, however, remains entirely unknown.</p><p><strong>Methods: </strong>Targeted Nup93 knockdown approaches were used in primary human endothelial cells to assess the role of Nup93 in endothelial RhoA/ROCK signaling and downstream readouts, including endothelial barrier function, cellular stiffness, and eNOS (endothelial NO synthase) function. Rescue studies include the use of pharmacological ROCK inhibitors and lentiviral-mediated Sun1 restoration methods. We additionally measure barrier function and vessel reactivity in our novel inducible endothelial-specific Nup93 mouse model.</p><p><strong>Results: </strong>Targeted loss of endothelial Nup93 significantly increases RhoA/ROCK activity for consequent endothelial permeability and decreased NO bioavailability both in vitro and in vivo. Mechanistically, we find that loss of Nup93 drastically reduces endothelial Sun1 levels for a concomitant increase in RhoA activity. Indeed, restoring Sun1 protein levels in Nup93-deficient endothelial cells mitigates RhoA activity, thereby rescuing both endothelial barrier function and eNOS expression.</p><p><strong>Conclusions: </strong>Taken together, we demonstrate endothelial Nup93 as a novel regulator of vascular permeability and NO-dependent vessel reactivity, contributing to the growing importance of nuclear membrane components in endothelial cell and vascular biology.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324964"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13371109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270047","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":"<i>NORAD</i> Overexpression Enhances hiPSC-CM Regenerative Potency via PUM2/<i>MASTL</i> Signaling.","authors":"Kanghui Huan, Yujian Jiang, Xin Xie, Weifeng Xu, Xiaolei Duan, Sai Yao, Yanli Cheng, Shaomeng Li, Yanfang Duan, Yingxin Yuan, Yeying Sun, Meng Zhao, Weihua Bian","doi":"10.1161/ATVBAHA.126.324431","DOIUrl":"10.1161/ATVBAHA.126.324431","url":null,"abstract":"<p><strong>Background: </strong>The engraftment of induced cells from human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for myocardial infarction therapy is critically hindered by their low cell-cycle activity and survival rates. In this study, we explored the role of the long noncoding RNA activated by DNA damage (<i>NORAD</i>) in enhancing the cell-cycle activity and engraftment of hiPSC-CMs, providing new insights into myocardial repair.</p><p><strong>Methods: </strong>hiPSC-CMs overexpressing <i>NORAD</i> (hiPSC-<i>NORAD</i>^OECMs) were generated via lentiviral transduction using a cardiac-specific promoter, whereas <i>NORAD</i> knockdown was achieved by small interfering RNA transfection. The effects of <i>NORAD</i> on cell-cycle activity, nuclear DNA content, nuclear number, maturation, and apoptosis in hiPSC-CMs were examined in vitro using Western blot, reverse transcription quantitative polymerase chain reaction, immunofluorescence, and flow cytometry. In a murine myocardial infarction model, hiPSC-CMs overexpressing <i>NORAD</i> were transplanted into the infarcted myocardium. Engraftment, cell-cycle activity, and infarct size were evaluated by immunofluorescence, and cardiac function was assessed by echocardiography. Furthermore, the molecular mechanisms underlying <i>NORAD</i>-mediated regulation of hiPSC-CM cell-cycle activity were investigated, including its role in exosome-mediated paracrine effects on host cardiomyocytes.</p><p><strong>Results: </strong><i>NORAD</i> overexpression significantly increased the percentages of Ki67 (antigen KI-67)-positive, PH3 (phosphorylated histone 3)-positive, Aurora B-positive, and EdU (5-ethynyl-2'-deoxyuridine)-positive cells. It also increased the proportion of diploid nuclei and mononucleated cells, induced a trend toward a less mature state, and reduced apoptosis in hiPSC-CMs. Transplantation of hiPSC-CMs overexpressing <i>NORAD</i> improved myocardial repair, with greater cell-cycle activity of engrafted cells and endogenous cardiomyocytes in the myocardial infarction model. Mechanistically, <i>NORAD</i> exerted its effects by sequestering PUM2 (pumilio RNA-binding protein family member 2), an RNA-binding protein, thereby alleviating its translational repression of <i>MASTL</i> (microtubule-associated serine/threonine kinase like), a key regulator of mitotic progression. Moreover, exosomes secreted by hiPSC-CMs overexpressing <i>NORAD</i> promoted the cell-cycle activity of recipient cardiomyocytes, suggesting a possible paracrine contribution to myocardial repair.</p><p><strong>Conclusions: </strong><i>NORAD</i> overexpression promoted cell-cycle progression via the PUM2/<i>MASTL</i> mRNA axis. Moreover, exosomes derived from these cells stimulated endogenous cardiomyocyte cell-cycle activity, contributing to myocardial repair. These findings underscore the therapeutic potential of <i>NORAD</i>-modulated hiPSC-CMs for promoting myocardial repair.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324431"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Resilience in Academic Science and Medicine.","authors":"Patricia K Nguyen, Paula Rodriguez-Miguelez, Mabruka Alfaidi, Ebru Erbay, Julie K Freed, Laura Hansen, Zamaneh Kassiri, Hong S Lu, Suellen Darc Oliveira, Albert W Wu, Hanrui Zhang, Zhen Bouman Chen","doi":"10.1161/ATVBAHA.126.324592","DOIUrl":"10.1161/ATVBAHA.126.324592","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324592"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366810","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":"Extracellular Mitochondria Mediate Endothelial Injury After Traumatic Brain Injury.","authors":"Lujia Tang, Yafan Liu, Kaifeng Pang, Yang Li, Yichi Zhang, Xiaoxi Lu, Xiaoyang Zhang, Pengbo Zhao, Zijian Zhou, Hao Zhang, Tianrui Ma, Junrui Liu, Ying Fu, Ming Wei, Jianning Zhang, Jing-Fei Dong, Zilong Zhao","doi":"10.1161/ATVBAHA.126.323502","DOIUrl":"10.1161/ATVBAHA.126.323502","url":null,"abstract":"<p><strong>Background: </strong>Local and systemic endothelial dysfunction following traumatic brain injury (TBI) results in secondary cerebral and pulmonary edema, tissue ischemia, and inflammation. However, the underlying mechanism of the endothelial dysfunction beyond the site of the primary trauma remains poorly understood. Morphologically intact and metabolically active extracellular mitochondria (exMt) accounted for 55.2% of brain-derived extracellular vesicles found in the peripheral blood of mice subjected to severe TBI. This observation led us to investigate the role of exMt in TBI-induced secondary endothelial injury.</p><p><strong>Methods: </strong>We measured circulating exMt in patients with TBI and mice subjected to TBI and examined the effects of exMt on endothelial cells in vitro and in vivo. Mechanistic studies involved evaluating Cavin-1-dependent endocytosis of exMt and its downstream effects on endothelial cells, including mitophagy activation, lysosomal dysfunction, and apoptosis. The findings were validated in Cavin-1 knockdown endothelial cells and Cavin-1-deficient mice.</p><p><strong>Results: </strong>Here, we report the detection of high levels of exMt in the peripheral blood samples from patients with TBI. These circulating exMt bound to and were endocytosed by endothelial cells via a Cavin-1-dependent pathway. exMt activated endothelial cells, caused vascular leakage, and promoted an inflammatory response in vitro. Furthermore, noninjured mice infused with exMt developed similar changes in the brain and lungs. exMt endocytosed by endothelial cells activated mitophagy and promoted the formation of mitophagosomes but impaired lysosomal function, leading to endothelial cell apoptosis.</p><p><strong>Conclusions: </strong>Results from this study demonstrate a novel subcellular mechanism for exMt-induced endothelial dysfunction during acute TBI.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e323502"},"PeriodicalIF":8.8,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315316","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}