Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"Prior Venous Thromboembolism Defines Distinct Genetic and Molecular Phenotypes in Chronic Thromboembolic Pulmonary Hypertension.","authors":"Zhu Zhang, Mengjie Duo, Xiaofan Ji, Bingzhang Zou, Haobo Li, Kuangxun Li, Huiwen Li, Yuhan Li, Yishan Li, Xincheng Li, Jixiang Liu, Yu Zhang, Wenxin Duan, Jianmin Lu, Huizhao Liao, Ran Miao, Peiran Yang, Shuai Zhang, Athiththan Yogeswaran, Ruifang Li-Gao, Astrid van Hylckama Vlieg, Frederikus A Klok, Suzanne C Cannegieter, Lan Zhao, Wanmu Xie, Cheng Hong, Zhenguo Zhai, Chen Wang","doi":"10.1161/ATVBAHA.126.325037","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.325037","url":null,"abstract":"<p><strong>Background: </strong>Chronic thromboembolic pulmonary hypertension (CTEPH) has traditionally been considered a long-term complication of pulmonary embolism. However, a substantial proportion of patients have no history of venous thromboembolism (VTE), suggesting underlying biological heterogeneity.</p><p><strong>Methods: </strong>We analyzed clinical and imaging characteristics of 712 patients with CTEPH stratified by prior VTE history. Whole-genome sequencing was performed in all patients and 2952 healthy controls to assess common variants. Bulk RNA sequencing of pulmonary endarterectomy tissues and plasma protein quantification were integrated to identify and validate subgroup-specific molecular signatures, with further validation in tissue and primary endothelial cells.</p><p><strong>Results: </strong>Patients with CTEPH and prior VTE (n=576, 80.9%) exhibited a distinct thrombotic phenotype with more proximal disease distribution (92.5% versus 66.2%) and greater likelihood of undergoing pulmonary endarterectomy (22.6% versus 3.7%). Genome-wide association study in CTEPH-VTE(+) patients versus controls identified coagulation-related loci at <i>ABO</i> (rs676996, <i>P</i>=1.1×10^-9) and <i>FGG</i> (rs7681423, <i>P</i>=2.5×10^-8), with high genetic correlation with pulmonary embolism (rg=0.52, <i>P</i>=0.028). In contrast, no consistent genomic signal was identified in patients without prior VTE. Integrative multiomics (transcriptome-wide association study, MAGMA, and bulk RNA sequencing differential expression analysis) convergently prioritized <i>CTSS</i> (cathepsin S) as a key molecular candidate in CTEPH-VTE(+). CTSS was consistently elevated in plasma, pulmonary endarterectomy tissue, and primary endothelial cells from CTEPH-VTE(+) patients and promoted endothelial proliferation via ERK signaling, which was attenuated by the selective <i>CTSS</i> inhibitor LY3000328.</p><p><strong>Conclusions: </strong>Stratification by prior VTE history reveals biologically distinct CTEPH phenotypes with divergent genetic architectures and identifies cathepsin S as a genetically nominated therapeutic target for thrombosis-associated pulmonary vascular remodeling.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190899","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":"Human Genetics of Adipose Dysfunction: Genomic Mechanisms and Therapeutic Opportunities in Cardiometabolic Disease.","authors":"Elizabeth A Burton, Victor Svenstrup, Mayank Murali, Hesam Dashti, Ruth J F Loos, Melina Claussnitzer","doi":"10.1161/ATVBAHA.126.324811","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.324811","url":null,"abstract":"<p><p>Cardiometabolic diseases are a leading cause of global morbidity and mortality and arise from shared and distinct risk factors acting through interconnected biological pathways. Although excess adiposity is a major risk factor, body mass index incompletely captures cardiometabolic risk, reflecting heterogeneity in overall and regional fat storage capacity and ectopic lipid accumulation. Failure of subcutaneous adipose tissue to expand appropriately promotes lipid overflow into visceral and ectopic depots, contributing to insulin resistance, dyslipidemia, and organ dysfunction. Human genetic studies have identified thousands of genetic loci influencing fat storage, fat distribution, and ectopic lipid accumulation, revealing that these traits reflect distinct underlying mechanisms with divergent cardiometabolic consequences. Recent scaling of genetic discovery for refined adiposity and cardiometabolic phenotypes and multitrait genetic approaches have advanced understanding of adipose-driven disease heterogeneity. We highlight variant-to-function strategies to resolve causal pathways and discuss emerging scalable approaches to accelerate biological learning from genetic discovery and translate these insights into adipose-directed therapeutics for cardiometabolic disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190909","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":"Magnetic Particle Imaging of Macrophage Phagocytosis Evaluates Plaque Vulnerability and Therapeutic Efficacy in Atherosclerosis.","authors":"Wei Tong, Ying Han, Yuxing Chen, Rundu Chen, Lei Gao, Hui Hui, Jie Tian, Yundai Chen","doi":"10.1161/ATVBAHA.126.325404","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.325404","url":null,"abstract":"<p><strong>Background: </strong>Developing new atherosclerosis therapeutics remains challenging. A noninvasive imaging method to assess plaque vulnerability is needed to provide early efficacy readouts and help select promising candidates for clinical trials. We aimed to identify macrophage phagocytosis markers associated with plaque vulnerability and evaluate whether magnetic particle imaging (MPI) of phagocytic activity can detect therapeutic responses and changes in plaque instability.</p><p><strong>Methods: </strong>Integrated transcriptomic and immunofluorescence staining analyses of human carotid plaques were conducted to identify key phagocytosis-related markers. A novel polyethylene glycol-coated superparamagnetic iron oxide nanoparticle (PESPION) was synthesized and characterized alongside comparator agents (Vivotrax and ferumoxytol). Vulnerable plaques were induced in ApoE^-/- mice by cast placement over the carotid artery. After 10-week treatment with a proprotein convertase subtilisin/kexin type 9 inhibitor (inclisiran) or a sodium-glucose cotransporter-2 inhibitor (empagliflozin), macrophage phagocytosis and plaque vulnerability were assessed by PESPION-enhanced MPI and histopathology, respectively. Comparisons between PESPION-enhanced MPI and magnetic resonance imaging were performed in proprotein convertase subtilisin/kexin type 9 inhibitor-treated and saline-control mice at 4 and 10 weeks.</p><p><strong>Results: </strong>MSR1 (macrophage scavenger receptor 1) was identified as a phagocytosis marker associated with plaque vulnerability. Compared with Vivotrax and ferumoxytol, PESPION exhibited a larger core size, superior serum stability, enhanced MPI performance, and greater macrophage uptake, which was blocked by MSR1 inhibition. In vivo, PESPION-enhanced MPI sensitively detected vulnerable plaques, with signals reduced on MSR1 inhibition. Inclisiran and empagliflozin reduced MPI-quantified phagocytic activity compared with controls. MPI signals correlated positively with plaque area and macrophage infiltration, negatively with smooth muscle cell content, and predicted the vulnerability index. Direct comparison with magnetic resonance imaging revealed that MPI detected therapeutic responses earlier (4 weeks) than T2*-weighted magnetic resonance imaging (10 weeks).</p><p><strong>Conclusions: </strong>MSR1 is a phagocytosis-related molecule associated with plaque vulnerability. PESPION-enhanced MPI provides a sensitive, noninvasive tool for quantifying MSR1-mediated macrophage phagocytosis, enabling robust evaluation of plaque vulnerability and pharmacological response.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190956","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":"AI and Deep Learning in Cardiovascular Imaging: From Risk Stratification to Precision Phenotyping.","authors":"Kaiyue Diao, Jiahua Lu, Alexander Dimitrakakis, Zelong Liu, Zahi A Fayad, Hao-Chih Lee, Xueyan Mei","doi":"10.1161/ATVBAHA.126.324762","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.324762","url":null,"abstract":"<p><p>Cardiovascular imaging plays a central role in the diagnosis, risk stratification, and management of cardiovascular disease, yet the complexity and volume of imaging data increasingly exceed the capacity of conventional interpretation. Artificial intelligence (AI) and deep learning offer new tools to extract quantitative, prognostic, and phenotypic information from routine cardiovascular images. This review summarizes the fundamentals of AI and deep learning, including model architectures, training strategies, and their relevance to cardiovascular imaging, followed by a focused discussion of current applications across chest radiography, chest computed tomography, computed tomography angiography/cardiac computed tomography, cardiac magnetic resonance imaging, echocardiography, and nuclear cardiology imaging. Studies were selected with emphasis on original investigations, large cohort analyses, and external validation studies reflecting current applications of AI in cardiovascular risk stratification and precision phenotyping. Across these modalities, AI applications in automated image processing and analysis have become relatively mature. Multiple multicenter and real-world studies have validated their value in improving efficiency and supporting cardiovascular management. Approaches that move beyond conventional human-defined imaging metrics to infer cardiovascular risk and disease phenotype remain at an earlier stage, requiring further standardization, validation, and clinical evaluation. AI is expanding the role of cardiovascular imaging from visual interpretation toward integrated assessment for risk stratification and precision phenotyping, though further work is needed to confirm generalizability and real-world performance before these tools can guide individual patient management.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190822","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":"Cardiomyocyte-Specific LncRNA CSTPP Prolongs the Proliferation Window by Promoting CDKN1A Decay in Postinfarction Cardiac Regeneration.","authors":"Ji-Dong Chen, Xi-Yan Lin, Xiao-Lu Yang, Wen-Zi Xu, Wan-Wen Cheng, Ying-Xin Mai, Yan-Yi Chen, Cheng-Lin Zhang, Kunfu Ouyang, Yue-Heng Wu, Bo Dai, Jie Liu","doi":"10.1161/ATVBAHA.126.325434","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.325434","url":null,"abstract":"<p><strong>Background: </strong>Adult mammalian cardiomyocytes exhibit some capacity to reenter the cell cycle after ischemic injury. However, activated cardiomyocytes rapidly undergo cell cycle rearrest shortly after activation. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of cardiac regeneration; however, their involvement in the process of cell cycle rearrest remains unexplored.</p><p><strong>Methods: </strong>Bulk RNA-sequencing was used to screen for lncRNAs differentially expressed during myocardial injury. Loss- and gain-of-function approaches were used to assess the role of lncRNA in cardiomyocyte proliferation and cardiac regeneration after myocardial infarction (MI). RNA pulldown and RNA immunoprecipitation were used to elucidate the underlying regulatory mechanisms.</p><p><strong>Results: </strong>We identified a cardiomyocyte-specific lncRNA downregulated after myocardial injury and named it cardiomyocyte-specific transcript promoting proliferation (CSTPP). CSTPP overexpression enhanced neonatal rat ventricular myocyte proliferation, whereas its knockdown exerted the opposite effects. In vivo, CSTPP deletion attenuated cardiomyocyte proliferation, leading to exacerbated cardiac dysfunction post-MI. Conversely, CSTPP overexpression promoted cardiomyocyte proliferation and improved cardiac function. Furthermore, CDKN1A (cyclin-dependent kinase inhibitor 1A) was found to be upregulated in cardiomyocytes localized at the border zone after MI, which was aggravated by CSTPP knockout and abrogated by CSTPP overexpression. Mechanistically, we showed that CSTPP interacts with YBX1 (Y box-binding protein 1), reinforcing the interaction between YBX1 and UPF1 (upstream frameshift 1), thereby enhancing UPF1 recruitment to CDKN1A mRNA and accelerating its decay. Notably, CSTPP was downregulated in heart samples from patients with MI. CSTPP overexpression decreased CDKN1A expression and facilitated proliferation in human induced pluripotent stem cell-derived cardiomyocytes.</p><p><strong>Conclusions: </strong>Our findings identified CSTPP as a cardiomyocyte-specific lncRNA that functions to extend the activation window of the cardiomyocyte cell cycle after MI by stabilizing the YBX1-UPF1 interaction and thus facilitating the UPF1-mediated decay of CDKN1A mRNA. These results establish CSTPP as a promising therapeutic target for cardiac regeneration after MI.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190799","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":"Short-Term Dietary Exposures and Thrombin Generation in Tanzanian Men: Exploratory Coagulation-Focused Analysis of a Randomized Dietary-Switch Trial.","authors":"Eka Patricia Kisali, Mark Roest, Tal Pecht, Ilaria De Simone, Vesla I Kullaya, Mary Vincent Mosha, Philip de Groot, Reginald A Kavishe, Mihai G Netea, Godfrey S Temba, Quirijn de Mast","doi":"10.1161/ATVBAHA.126.325420","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.325420","url":null,"abstract":"<p><strong>Background: </strong>Rapid dietary transitions in sub-Saharan Africa may alter coagulation profiles; however, this remains poorly characterized.</p><p><strong>Methods: </strong>An open-label dietary-intervention trial in Tanzania enrolled 77 healthy men aged 20 to 40 years. They underwent 1 of 3 interventions (n=22 per arm): heritage-to-Western-style diet switch (2 weeks), Western-to-heritage diet switch (2 weeks), or continued their habitual Western-style diet with daily consumption of 1 L of a traditional fermented banana-millet beverage (Mbege) for 1 week. The 2 diet-switch arms had 5 habitual-diet controls each, while the Mbege arm had no parallel control group. Plasma was collected at baseline, postintervention, and 4-week follow-up. We quantified plasma coagulation proteins and assessed thrombin and plasmin generation. Coagulation analyses were prespecified secondary end points but are interpreted as exploratory because no formal coagulation outcome hierarchy was prespecified.</p><p><strong>Results: </strong>In control-adjusted analyses, the heritage-to-Western-style diet switch was associated with higher endogenous thrombin potential at 5 pM recombinant tissue factor postintervention compared with baseline (fold-change ratio, 1.19 [95% CI, 1.01-1.41]; nominal <i>P</i>=0.037). Prothrombin increased within the heritage-to-Western intervention arm (98.0%-104.5%; <i>P</i>_FDR=0.027), but not relative to habitual-diet controls (fold-change ratio, 1.05 [95% CI, 0.93-1.18]; <i>P</i>=0.443). In the uncontrolled Mbege arm, fibrinogen, prothrombin, FVIII (factor VIII), and antithrombin decreased, while endogenous thrombin potential at 1 pM recombinant tissue factor increased. The Western-style-to-heritage diet switch showed limited consistent changes in coagulation readouts.</p><p><strong>Conclusions: </strong>Short-term dietary westernization was associated with higher control-adjusted endogenous thrombin potential at 5 pM recombinant tissue factor, while the within-arm increase in prothrombin did not remain significant relative to controls. The uncontrolled Mbege arm showed a distinct pattern, with lower plasma concentrations of several coagulation proteins but higher endogenous thrombin potential at 1 pM recombinant tissue factor. These findings suggest that short-term dietary exposures may influence thrombin generation. However, given the small control groups, uncontrolled Mbege arm, and nonisocaloric design, these results are exploratory and require confirmation in larger controlled studies.</p><p><strong>Registration: </strong>URL: https://www.isrctn.com/ISRCTN15619939?; Unique identifier: ISRCTN15619939.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126344","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":"Wearable Sensors and Remote Patient Monitoring in Cardiovascular Disease: From Continuous Physiological Surveillance to Actionable Insights.","authors":"Ahmed Tariq, Wonbum Sohn, Yoon Jae Lee, Yun Soung Kim","doi":"10.1161/ATVBAHA.126.324766","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.324766","url":null,"abstract":"<p><p>Wearable technologies are increasingly used to support cardiovascular care by enabling continuous physiological monitoring beyond conventional clinical environments. Advances in consumer and medical-grade devices have expanded cardiovascular surveillance from intermittent assessments to longitudinal monitoring of heart rhythm, heart rate variability, blood pressure, heart failure status, and other physiological parameters. Concurrent advances in artificial intelligence have enhanced the ability of wearable systems to extract clinically meaningful insights from large-scale physiological data, supporting earlier disease detection, risk stratification, and personalized intervention. In this review, we examine the evolving role of wearable technologies across a 3-stage framework of cardiovascular care: surveillance, diagnosis, and intervention. We discuss established platforms, including wearable electrocardiography, photoplethysmography-based monitoring, and wearable cardioverter-defibrillators, alongside emerging modalities such as wearable ultrasound, seismocardiography, multimodal sensor fusion, and closed-loop therapeutic systems. We further highlight major technological trends, including the diversification of sensing modalities, the growing integration of artificial intelligence, and the transition from passive monitoring toward autonomous intervention. Finally, we discuss current challenges related to validation, clinical implementation, equity, privacy, and regulatory oversight. Together, these developments point toward a future in which wearable and multimodal sensing, artificial intelligence, and clinical workflows are increasingly integrated into cardiovascular disease prevention, diagnosis, and management.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126361","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":"LncRNA <i>TAAL</i> Regulates TIE1-Mediated Vascular Remodeling and Is Associated With Diabetic Retinopathy.","authors":"Gyan Ranjan, Samriddhi Arora, Sarmeela Sharma, Rahul C Bhoyar, Vigneshwar Senthivel, Ritesh Narula, Vinod Scaria, Subhabrata Chakrabarti, Inderjeet Kaur, Sridhar Sivasubbu, Rajender K Motiani","doi":"10.1161/ATVBAHA.126.324094","DOIUrl":"https://doi.org/10.1161/ATVBAHA.126.324094","url":null,"abstract":"<p><strong>Background: </strong>TIE1 is an endothelial receptor tyrosine kinase, which plays a crucial role in vascular development and remodeling, including in diseases such as diabetic retinopathy (DR). However, the molecular mechanisms and regulatory interactome governing TIE1 function remain largely unknown. Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulators of endothelial gene expression and vascular homeostasis, yet lncRNA regulators of TIE1 have not been characterized. This study was designed to identify lncRNA regulators of TIE1 and elucidate their functional roles in endothelial biology and DR pathogenesis.</p><p><strong>Methods: </strong>Using a protein-centric RNA immunoprecipitation sequencing approach in human umbilical vein endothelial cell/Tert2 cells, we identified a novel TIE1-interacting lncRNA. Functional characterization was performed via siRNA-mediated knockdown and plasmid-based overexpression, followed by assays for migration, proliferation, tube formation, permeability, calcium imaging, and cytoskeletal dynamics. Protein turnover was assessed by cycloheximide chase, proteasomal/lysosomal inhibition, and ubiquitin pulldown. Functional conservation was evaluated in zebrafish through morpholino knockdown and human-orthologue complementation. Clinical relevance was investigated in cadaveric retinal tissues (n=17 controls; n=14 diabetic) and peripheral blood samples from controls (n=60), diabetic without retinopathy (n=50), nonproliferative DR (n=70), and proliferative DR (n=50) participants, alongside a hyperglycemic zebrafish DR model.</p><p><strong>Results: </strong>We identified <i>TAAL</i>, which specifically interacts with TIE1 but not TIE2. <i>TAAL</i> regulated endothelial migration, proliferation, tube formation, and permeability by maintaining endoplasmic reticulum-calcium homeostasis and cytoskeletal dynamics. Mechanistically, <i>TAAL</i> negatively regulated TIE1 protein levels via ubiquitin-mediated degradation without altering <i>TIE1</i> mRNA expression. Its function was conserved in zebrafish, where <i>taal</i> knockdown produced angiogenic defects rescued by human <i>TAAL</i>. Under hyperglycemia, <i>TAAL</i> was downregulated in endothelial cells but upregulated in mixed retinal cultures, diabetic retinal tissues, and nonproliferative DR/proliferative DR patient blood, supporting biomarker potential. <i>TAAL</i> overexpression restored endothelial barrier integrity and VE-cadherin (vascular endothelial cadherin) localization in vitro and prevented vascular leakage in vivo in zebrafish.</p><p><strong>Conclusions: </strong><i>TAAL</i> regulates TIE1 protein turnover through ubiquitination and calcium-mediated vascular remodeling, exhibiting cell type-specific regulation under diabetic stress, positioning it as both a minimally invasive biomarker and therapeutic target for DR.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149126424","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":"Lipoprotein(a), Oxidized Phospholipids and Tensile Clot Strength Measured by Thromboelastography in Patients Undergoing Percutaneous Intervention.","authors":"Paul A Gurbel, Udaya S Tantry, Kevin P Bliden, William W Ashley, Young Hoon Jeong, Sotirios Tsimikas","doi":"10.1161/ATVBAHA.126.324402","DOIUrl":"10.1161/ATVBAHA.126.324402","url":null,"abstract":"<p><strong>Background: </strong>Lp(a) (lipoprotein[a]) and tensile clot strength (TCS) are distinct and independent risk factors for incident cardiovascular disease and recurrent ischemic events. Lp(a) is a carrier of oxidized phospholipids (OxPL) that contribute to its atherothrombotic properties. The current objective is to study the relationship of Lp(a) and OxPL biomarkers with TCS in patients with high-risk vascular diseases.</p><p><strong>Methods: </strong>In a subanalysis of the ongoing MBRACE trial (Multidisciplinary Approach to Reduce Cardiovascular Health Disparities in the Baltimore Racial Minority Communities), we studied Lp(a), OxPL biomarkers, and TCS in healthy subjects (n=17) and in patients with cardiovascular disease undergoing percutaneous intervention (multivessel coronary artery disease [n=60], myocardial infarction [n=86], and ischemic stroke [n=28]). Lp(a), OxPL-apoB, OxPL-apo(a), OxPL-plasminogen (OxPL-PLG), and total plasminogen were measured using enzyme-linked immunoassays. High Lp(a) was defined as ≥125 nmol/L. TCS was measured by thromboelastography, and hypercoagulability was defined by values ≥66.5 mm.</p><p><strong>Results: </strong>Compared with healthy subjects, patients had higher Lp(a), OxPL-apoB, OxPL-apo(a), and TCS (<i>P</i><0.05 for all). Black patients, compared with White patients, had higher Lp(a), OxPL biomarkers, and TCS (<i>P</i>≤0.05); whereas females had higher Lp(a) and OxPL biomarkers except OxPL-PLG (<i>P</i>≤0.03) and numerically higher TCS (<i>P</i>=0.06). Black females had the highest Lp(a), OxPL-apoB, OxPL-apo(a), and TCS (<i>P</i>≤0.05). In a multivariate analysis, hypercoagulability was associated with Lp(a), OxPL-apoB, and total plasminogen (<i>P</i>≤0.019), whereas high Lp(a) was associated with OxPL-apoB and OxPL-apo(a) (≤0.004).</p><p><strong>Conclusions: </strong>In patients with high-risk cardiovascular disease undergoing percutaneous intervention, Lp(a), OxPL-related biomarkers, and TCS are influenced by race and gender and correlated with hypercoagulability. These findings suggest novel mechanistic insights into the relationship between Lp(a), OxPL biomarkers, and the propensity for whole-blood clotting and may be relevant in explaining the outcomes of patients in ongoing trials targeting the reduction of Lp(a).</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT06168968.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324402"},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787557","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":"COPI Coatomer Regulates Several Steps of HDL Metabolism.","authors":"Grigorios Panteloglou, Paolo Zanoni, Christopher S Law, Brian Woods, Alaa Othman, Mustafa Yalcinkaya, Simon F Norrelykke, Andrzej J Rzepiela, Szymon Stoma, Michael Stebler, Anja Kerksiek, Michele Visentin, Marieke Smit, Justina Clarinda Wolters, Sofia Kakava, Anton Potapenko, Eveline Schlumpf, Silvija Radosavljevic, Stephanie Häusler, Marta Futema, Nawar Dalila, Anne Tybjaerg-Hansen, Steve E Humphries, Jan Albert Kuivenhoven, Bart van de Sluis, Dieter Lütjohann, Roger Meier, Jérôme Robert, Janet Chou, Raif S Geha, Anthony K Shum, Lucia Rohrer, Arnold von Eckardstein","doi":"10.1161/ATVBAHA.126.324616","DOIUrl":"10.1161/ATVBAHA.126.324616","url":null,"abstract":"<p><strong>Background: </strong>Reverse cholesterol transport by HDLs (high-density lipoproteins) is considered an antiatherogenic metabolic pathway. Hepatocytes are the main contributors to the efficacy of this pathway by the production of apoA-I (apolipoprotein A1) and its lipidation by ABCA1 (ATP-binding cassette transporter A1), selective uptake of cholesterol via SR-BI (scavenger receptor class B type 1), and uptake of entire HDL particles. The molecular determinants of the latter step are not well understood.</p><p><strong>Methods: </strong>We performed a genome-wide RNA interference screen for genes limiting the uptake of HDL fluorescently labeled at its protein moiety into Huh-7 hepatocarcinoma cells. Top hit genes were validated by targeted in vitro experiments and the analysis of associations between their variants and HDL-C (HDL-cholesterol) levels in the databases of the Global Lipids Genetics Consortium and the UK Biobank, as well as inborn errors of metabolism and their respective mouse models.</p><p><strong>Results: </strong>The knockdown of 128 genes significantly inhibited HDL uptake. Six of them encode components of the COPI (coat protein I) coatomer, namely, <i>COPA</i>, <i>COPB1</i>, <i>COPB2</i>, <i>COPG1</i>, <i>ARCN1</i>, and <i>COPZ1</i>. Knocking down any of them decreased the uptake of both fluorescently labeled proteins and lipids of HDL, the cell surface abundance of SR-BI, and <i>APOA1</i> expression and apoA-I secretion but increased the cell surface abundance of ABCA1. Common single-nucleotide polymorphisms of <i>ARCN1</i> and <i>COPB1</i> were associated with significantly higher HDL-C levels in the population, while rare <i>COPA</i> and <i>COPG1</i> variants causing immunopathies were associated with rather lower levels of HDL-C in both affected patients and the corresponding genetically modified mice.</p><p><strong>Conclusions: </strong>In hepatocytes, the COPI coatomer regulates HDL holoparticle uptake, selective lipid uptake, apoA-I secretion, and ABCA1 expression, and thereby, it influences plasma levels of HDL-C.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":"e324616"},"PeriodicalIF":8.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720098","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}