Arteriosclerosis, Thrombosis, and Vascular Biology最新文献

{"title":"⁶⁸Ga-DOTATATE Measurements Predict Progression of Aortic Valve Calcification in Humans.","authors":"Wesam Aldosoky, Shady Abohashem, Guillaume Goudot, Simran S Grewal, Iqra Qamar, Erin Hanlon, Omar Alani, Jamie Bellinge, Giovanni Civieri, Michael T Osborne, Marc R Dweck, Pedram Heidari, Ahmed Tawakol","doi":"10.1161/ATVBAHA.125.322779","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322779","url":null,"abstract":"<p><strong>Background: </strong>Inflammation potentiates aortic valve calcification (AVC). Gallium dodecane tetraacetic acid-Tyr3-octreotate (⁶⁸Ga-DOTATATE), a positron emission tomography tracer that binds to somatostatin receptors, provides a measure of tissue inflammation. However, the diagnostic and prognostic values of aortic valve (AV) ⁶⁸Ga-DOTATATE uptake in AVC remain unexplored. Here, we tested whether AV ⁶⁸Ga-DOTATATE uptake predicts the progression of AVC.</p><p><strong>Methods: </strong>A total of 683 individuals (median age, 63 years; 46% male) underwent clinical ⁶⁸Ga-DOTATATE positron emission tomography/computed tomography imaging from 2017 to 2023; 209 had follow-up imaging (median, 1.3 years interval). AV inflammation was measured as the maximum standardized uptake value of ⁶⁸Ga-DOTATATE uptake within the AV on baseline positron emission tomography/computed tomography. AVC was quantified on baseline and follow-up computed tomography scans (Hounsfield units >130). AVC progression was assessed as the difference between baseline and follow-up AVC. Individuals with a square root difference of annualized AVC change ≥2.5 were characterized as progressors and <2.5 as nonprogressors. Demographic and clinical data were collected from medical records.</p><p><strong>Results: </strong>Baseline AV ⁶⁸Ga-DOTATATE uptake correlated with baseline AVC (standardized ρ=0.12; <i>P</i>=0.002). Furthermore, baseline AV ⁶⁸Ga-DOTATATE uptake associated with AVC progression (odds ratio [OR], 3.0 [95% CI, 1.4-6.4]; <i>P</i>=0.004) and remained significant after separately adjusting for baseline AVC (OR, 3.1 [95% CI, 1.5-6.6]), sex (OR, 4.0 [95% CI, 1.7-9.0]), hypertension (OR, 2.8 [95% CI, 1.3-6.2]), diabetes (OR, 3.0 [95% CI, 1.4-6.4]), hyperlipidemia (OR, 2.4 [95% CI, 1.1-5.3]), smoking (OR, 3.1 [95% CI, 1.5-6.7]), chronic kidney disease (OR, 2.9 [95% CI, 1.4-6.3]), and body mass index (OR, 3.0 [95% CI, 1.4-6.3]), became insignificant when adjusting to age (OR, 1.9 [95% CI, 0.8-4.3]).</p><p><strong>Conclusions: </strong>Our study highlights the use of ⁶⁸Ga-DOTATATE for assessing AV inflammation and predicting AVC progression. These findings underscore the role of inflammation in AVC progression and have potential implications for risk assessment and evaluating therapies in AV disease.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249415","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":"Atf3 Deficiency Promotes Mesodermal Commitment and Enhances Endothelial Differentiation in Embryonic Stem Cells.","authors":"Zongyue Jiang, Lide Su, Cuiting Chen, Ronghai He, LiLi Jiang, Yanyan Shu, Dandan Dai, Man Wu, Ailin Guo, Jianlei Liu, Suhuan Liu, Zonghong Liu","doi":"10.1161/ATVBAHA.125.323063","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323063","url":null,"abstract":"<p><strong>Background: </strong>Ischemic diseases have become a major threat to global health, with endothelial cell (EC) damage closely associated with their pathogenesis and progression. Cell therapies targeting endothelial repair have thus become a treatment approach of great interest, yet the procurement of clinically approved ECs for these applications has not been fully established. Modulating the expression of Atf3 (activating transcription factor 3) represents a potential strategy for deriving ECs from stem cells; however, its precise function in the development and differentiation of ECs from stem cells remains elusive. In the present study, we sought to elucidate the potential role of Atf3 in the differentiation of embryonic stem cells into ECs.</p><p><strong>Methods: </strong>CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) system was used to knockout Atf3 (Atf3KO [Atf3 knockout]) in mouse embryonic stem cells. EC differentiation was initially induced using the hanging drop method to promote embryoid bodies formation, followed by embryoid bodies attachment onto culture slides. The expression changes of EC markers during differentiation were assessed by RNA sequencing, Western blotting, immunofluorescence staining, flow cytometry, and reverse transcription quantitative polymerase chain reaction. Functional comparisons of differentiated ECs were performed by assessing LDL (low-density lipoprotein) uptake and NO production. Potential molecular mechanisms were further explored via bioinformatic analysis of RNA sequencing data.</p><p><strong>Results: </strong>Atf3KO led to a significant upregulation in the expression levels of progenitor and mesoderm cell markers on days 3 and 6 of differentiation. By day 9, the expression of mature EC markers also exhibited a notable increase. Moreover, Atf3KO enhanced the functional properties of differentiated Atf3KO ECs. In addition, our findings revealed that the activation of the Rap1 signaling pathway, triggered by Atf3KO, contributed to ECs development and maturation.</p><p><strong>Conclusions: </strong>Atf3KO directs embryonic stem cells toward the mesodermal lineage and activates the Rap1 signaling pathway, thereby promoting ECs development. These findings highlight a key role of Atf3 in regulating early stage of vascular endothelial development.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249412","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":"Flow-Sensitive HEG1 Controls eNOS Activity to Prevent Endothelial Dysfunction, Hypertension, and Atherosclerosis.","authors":"Michael D Clark, Yerin Kim, Cesar A Romero, Dong Won Kang, Kyung In Baek, Eun Ju Song, Cailin E Kellum, Jay A Bowman-Kirigin, Christian Park, Ruei-Chun Hung, Leandro Choi, Vir Kapoor, Shoutaro Tsuji, Jennifer S Pollock, Hanjoong Jo","doi":"10.1161/ATVBAHA.125.323285","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323285","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249427","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":"Lung Lymphatics in Edema, Inflammation, and Thrombosis.","authors":"Chou Chou, Hasina Outtz Reed","doi":"10.1161/ATVBAHA.125.322486","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322486","url":null,"abstract":"<p><p>The lung lymphatics are formed from lymphatic endothelial cells and play a pivotal role in lung fluid homeostasis and immune trafficking. Though blood vascular function in the lung has long been an area of active investigation, many aspects of lung lymphatic vascular function have only recently been uncovered. In this review, we will discuss our current knowledge of lung lymphatic function and how these vessels differ from lung blood vasculature in their architecture, function, and response to injury in 3 domains: edema, inflammation, and thrombosis. We will review the rich historical anatomic literature that described the lung lymphatics in great detail and elucidated foundational discoveries that continue to shape our current understanding of the lung lymphatics, even in the molecular era. We conclude by highlighting key questions for the field of lung lymphatic biology.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249447","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":"Imaging Findings Associated With Socioenvironmental Exposures Inform Mechanisms of Cardiovascular Disease.","authors":"Shady Abohashem, Fatima Saeed, Thomas Münzel, Sadeer Al Kindi, Borek Foldyna, Zahi A Fayad, Ahmed Tawakol, Michael T Osborne","doi":"10.1161/ATVBAHA.125.322470","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322470","url":null,"abstract":"<p><p>Cardiovascular disease remains the leading cause of mortality worldwide, driven by risk factors that range from traditional (eg, hypertension, hyperlipidemia) to less recognized socioenvironmental contributors. These broader exposures include adverse socioeconomic status, air and noise pollution, attributes of the built environment, and ambient temperatures, among others, which exert complex mechanistic influences that often involve neural-autonomic-immune pathways that promote traditional cardiovascular disease risk factors and atherosclerosis. Advanced noninvasive imaging modalities, including positron emission tomography, computed tomography, magnetic resonance imaging, and ultrasound, allow for assessment of subclinical vascular changes, such as arterial inflammation and plaque burden, as well as assessments of changes in other organs, including the brain and inflammatory tissues, that associate with these exposures and have the potential to clarify the mechanisms of exposure-related pathology. This review synthesizes current evidence from multimodality imaging studies linking socioeconomic status, air pollution, noise, and other environmental exposures to imaging markers of cardiovascular disease. These findings suggest opportunities to deeply characterize underlying mechanisms, refine risk assessment, prioritize targeted interventions, and inform policies aimed at mitigating adverse exposures. Through this framework, we aim to catalyze a broader approach to preventing cardiovascular disease that recognizes the profound interplay among the social, environmental, and biological determinants of health.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249449","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":"Molecular ART in the Atherosclerotic Lesion: ADP-Ribosylation.","authors":"Jenny E Kanter, Tomas Vaisar","doi":"10.1161/ATVBAHA.125.323694","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323694","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205055","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":"Metabolic Axis of Vulnerability: Lessons From MR Vessel Wall Imaging.","authors":"Luca Saba","doi":"10.1161/ATVBAHA.125.323643","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.323643","url":null,"abstract":"","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205067","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":"Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.","authors":"Lei Zheng, Zhenxi Zhang, Yutong Liu, Chen Cheng, Biao Zhao, Run Ji, Zhipeng Chen, Liu Yang, Jing Cai, Kuanyu Li, Tong Qiao","doi":"10.1161/ATVBAHA.125.322495","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322495","url":null,"abstract":"<p><strong>Background: </strong>Low wall shear stress (WSS) at arterial bifurcations and curves damages endothelial cells, promoting the development of atherosclerosis. Although the accumulation of iron in plaques has been observed, the mechanisms behind it and its effects are not fully understood.</p><p><strong>Methods: </strong>Detect the iron content in different parts of the mouse partial carotid artery ligation model and the aorta. The chelating iron therapy was used to assess the impact of low WSS-induced iron accumulation and atherosclerosis in the arterial wall. In vitro experiments utilized human umbilical vein endothelial cells and an orbital-shaker model to simulate WSS. Mice with endothelial cell-specific knockout of IRP2 (iron regulatory protein 2) and deletion of Apoe (<i>Apoe</i>^<i>-/-</i><i>IRP2</i>^<i>iEcko</i>) were constructed, as well as a human umbilical vein endothelial cell line with <i>IRP2</i> knockdown.</p><p><strong>Results: </strong>We investigated the iron accumulation induced by low WSS in carotid arteries. Hinokitiol, an iron chelator, was found to reduce this iron buildup and decrease the progression of atherosclerosis. Low WSS in the carotid arteries led to chronic iron accumulation, which altered the expression of iron metabolism-related proteins in endothelial cells, particularly IRP2. Knocking down <i>IRP2</i> in endothelial cells resulted in an increase in the expression of inflammation-related proteins and a significant elevation in the expression of HIFs (hypoxia-inducible factors). <i>Apoe</i>^<i>-/-</i><i>IRP2</i>^<i>iEcko</i> mice exhibited an increased susceptibility to atherosclerosis. The use of HIF inhibitors, PX-478 and PT-2385, was able to suppress the exacerbation of atherosclerosis in <i>Apoe</i>^<i>-/-</i> mice caused by the endothelial cell-specific knockout of <i>IRP2</i>.</p><p><strong>Conclusions: </strong>Our results indicate that low WSS-induced endothelial cell iron metabolism abnormalities, by inducing arterial wall iron accumulation and abnormal expression of iron metabolism-related proteins, promote the occurrence and development of atherosclerosis. The use of iron chelators can alleviate the onset and progression of low WSS-induced atherosclerosis.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205120","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":"Pharmacological Inhibition of Ferroptosis Attenuates Experimental Abdominal Aortic Aneurysm Formation.","authors":"Jonathan R Krebs, Paolo Bellotti, Walker Ueland, Jeff Arni C Valisno, Denny Joseph Manual Kollareth, Shiven Sharma, Gang Su, Joseph B Hartman, Aravinthan Adithan, Michael Spinosa, Manasi Kamat, Timothy Garrett, Guoshuai Cai, Ashish K Sharma, Gilbert R Upchurch","doi":"10.1161/ATVBAHA.125.323269","DOIUrl":"10.1161/ATVBAHA.125.323269","url":null,"abstract":"<p><strong>Background: </strong>The pathogenesis of abdominal aortic aneurysm (AAA) formation involves vascular inflammation, thrombosis formation, and programmed cell death, leading to aortic remodeling. In this study, we deciphered the role of ferroptosis, an excessive iron-mediated cell death in macrophages during aortic inflammation and vascular remodeling in AAA formation.</p><p><strong>Methods: </strong>Single-cell RNA sequencing analysis was performed on the human AAA tissue database. AAAs were induced in male and female C57BL/6 (wild-type) mice using 2 models with topical elastase or elastase+β-aminopropionitrile, with or without liproxstatin-1, a specific ferroptosis inhibitor, treatment. Aortic diameter, cytokine expression, histology, hallmarks of ferroptosis such as lipid peroxidation and glutathione, and lipid analysis using mass spectrometry were measured in aortic tissue extracts. In vitro studies deciphered the crosstalk of macrophages and smooth muscle cells and analyzed ferroptosis and MMP (matrix metalloproteinase) expressions.</p><p><strong>Results: </strong>Single-cell RNA sequencing analysis demonstrated significant differences in ferroptosis-related genes in macrophages from human AAAs compared with control aortic tissue. Using 2 established murine models of AAA and aortic rupture in wild-type mice, we observed that treatment with liproxstatin-1 significantly attenuated aortic diameter, proinflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption, and increased smooth muscle cell α-actin expression compared with untreated mice. Lipidomic analysis using mass spectrometry shows a significant increase in ceramides and a decrease in intact lipid species levels in murine AAA tissue compared with controls in the murine AAA model. Mechanistically, in vitro studies demonstrate that liproxstatin-1 treatment of macrophages mitigated ferroptosis and MMP9 expression, as well as the crosstalk with aortic smooth muscle cells by downregulating MMP2 secretion.</p><p><strong>Conclusions: </strong>Taken together, this study demonstrates that pharmacological inhibition by liproxstatin-1 mitigates macrophage-dependent ferroptosis, contributing to the inhibition of aortic inflammation and remodeling during AAA formation.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205301","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":"Influence of Weight Loss and Weight Regain on Adipose Tissue Inflammation.","authors":"Lourdes Caceres, Aleepta Guha Ray, Margo P Emont, Ada Weinstock","doi":"10.1161/ATVBAHA.125.322196","DOIUrl":"https://doi.org/10.1161/ATVBAHA.125.322196","url":null,"abstract":"<p><p>The global rise in obesity underscores the urgent need for effective long-term weight-management strategies. Weight loss (WL) is extremely beneficial in combating obesity complications, justifying the great success of recent WL medications. However, most individuals trying to lose weight will fail to maintain a lower body weight. Weight regain following WL increases the risk of cardiovascular disease and mortality. Adipose tissue inflammation is a critical mediator of metabolic dysfunction in obesity, contributing to cardiovascular complications. In obesity, chronic low-grade inflammation, marked by immune infiltration and dysregulated adipocyte function, contributes to systemic insulin resistance and metabolic comorbidities. However, the adipose tissue response to WL and subsequent weight regain is distinct from that in non-weight-fluctuating obesity and far less studied. This review synthesizes current literature to elucidate the dynamic shifts in adipose tissue across the continuum of obesity, WL, and weight regain.</p>","PeriodicalId":8401,"journal":{"name":"Arteriosclerosis, Thrombosis, and Vascular Biology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205088","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}