Circulation最新文献

{"title":"Correction to: Sedentary Behavior and Light-intensity Physical Activity During Pregnancy and Cardiovascular Health: A Science Advisory From the American Heart Association.","authors":"Kara M Whitaker, Bethany Barone Gibbs, Marie-France Hivert, Nour Makarem, Elizabeth Moxley, Jason Vaught, Kelly R Evenson","doi":"10.1161/CIR.0000000000001340","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001340","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 19","pages":"e1000"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975429","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":"Prompting Introspection.","authors":"Jacqueline Baras Shreibati","doi":"10.1161/CIRCULATIONAHA.125.074009","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.074009","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 19","pages":"1375-1377"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993303","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":"Revisiting the Open Vein Hypothesis to Reduce the Postthrombotic Syndrome: Implications for Multidisciplinary Care and Research: A Scientific Statement From the American Heart Association.","authors":"Wenzhu Li,Suresh Vedantham,Farouc A Jaffer,Stavros K Kakkos,Jean-Philippe Galanaud,Paul P Dobesh,Eri Fukaya,Mary O Whipple,Olamide Alabi,Rachel P Rosovsky,Peter K Henke,","doi":"10.1161/cir.0000000000001330","DOIUrl":"https://doi.org/10.1161/cir.0000000000001330","url":null,"abstract":"The \"open vein hypothesis\" postulates that early thrombus clearance and restoration of venous blood flow may prevent postthrombotic syndrome after proximal deep vein thrombosis. Since its proposal several decades ago, new insights from basic and clinical studies have motivated a re-evaluation and refinement of this hypothesis. According to data from these studies, susceptibility to postthrombotic syndrome occurs as a result of differences in genetic composition, thrombophilic conditions, predilection to inflammation and fibrosis, endogenous fibrinolytic capability, timing of s ymptom presentation and treatment initiation, and efficacy of antithrombotic therapy. Although initial restoration of an open vein appears to be beneficial for selected patient groups, freedom from postthrombotic syndrome is more likely in the setting of long-term venous patency, reduced recurrent thrombotic episodes, and reduced perithrombotic (eg, vein wall and valve) inflammation. These underlying biological mechanisms need further elucidation, with a long-term goal of personalizing treatment by mapping the individuals' clinical presentation with their underlying risk factors and assessing time-dependent biological processes that occur as a clinical venous thrombosis resolves. This scientific statement (1) highlights historical fundamentals of the open vein hypothesis and then showcases new research insights into the pathophysiological factors driving postthrombotic syndrome; (2) discusses advantages and disadvantages of imaging modalities for deep vein thrombosis used in clinical practice, including the potential to depict thrombus chronicity and status of vein wall injury; (3) proposes measures to develop integrated multidisciplinary care for deep vein thrombosis focused on the reduction of postthrombotic syndrome; and (4) identifies priority areas and questions for further research.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"8 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945132","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":"Targeting uPARAP Modifies Lymphatic Vessel Architecture and Attenuates Lymphedema.","authors":"Fabrice Gucciardo, Alizée Lebeau, Sébastien Pirson, Florence Buntinx, Elitsa Ivanova, Silvia Blacher, Pascal Brouillard, Jonathan Deroye, Louis Baudin, Alexandra Pirnay, Florent Morfoisse, Claire Villette, Christophe Nizet, François Lallemand, Carine Munaut, Kari Alitalo, Liesbet Geris, Miikka Vikkula, Marine Gautier-Isola, Agnès Noel","doi":"10.1161/CIRCULATIONAHA.124.072093","DOIUrl":"10.1161/CIRCULATIONAHA.124.072093","url":null,"abstract":"<p><strong>Background: </strong>Lymphedema is an incurable disease associated with lymphatic dysfunction that causes tissue swelling and fibrosis. We investigated whether lymphedema could be attenuated by interfering with uPARAP (urokinase plasminogen activator receptor-associated protein; <i>Mrc2</i> gene), an endocytic receptor involved in fibrosis and lymphangiogenesis.</p><p><strong>Methods: </strong>We generated mice with lymphatic endothelial cell (LEC)-specific <i>uparap</i> deficiency and compared them with constitutive knockout mice by applying a preclinical model of secondary lymphedema (SL). Computerized methods were applied for 2-dimensional and 3-dimensional image quantifications. Cellular effects of uPARAP deletion on lymphatic permeability were assessed by small interfering RNA-mediated silencing in human dermal LECs and a pharmacologic treatment targeting ROCK (Rho-associated coiled coil containing kinase), an established regulator of cell junctions. The uPARAP and vascular endothelial cadherin partnership was investigated through proximity ligation assay, coimmunoprecipitation, and immunostaining. An in silico model was generated to analyze the fluid-absorbing function of the lymphatic vasculature. To interfere with uPARAP, its downregulation was achieved in vivo through a gapmer approach.</p><p><strong>Results: </strong><i>uparap</i> deficiency mitigated several key pathologic features of SL, including hindlimb swelling, epidermal thickening, and the accumulation and size of adipocytes. In both global and LEC-conditional <i>uparap</i>-deficient mice, induction of SL led to a distinctive labyrinthine vasculature, defined herein by twisted and hyperbranched vessels with overlapping cells. This topology, mainly composed of pre-collecting vessels, correlated with reduced SL, but not with change in fibrosis, highlighting the importance of uPARAP in regulating LEC functions in a lymphedematous context. In vitro, uPARAP knockdown in LECs impaired vascular endothelial growth factor C-mediated endosomal trafficking of vascular endothelial cadherin and induced overlapping cell junctions. The pharmacologic inhibition of ROCK recapitulated cell superimposition in vitro and the labyrinthine vasculature in vivo with attenuated SL. Computational modeling of labyrinthine lymphatic vasculature supported the observation on their improved fluid-absorbing function in comparison with a normal hierarchic network. These data provide proof of concept of inducing a labyrinthine topology to treat SL. For therapeutic purposes, we validated the use of an anti-uPARAP gapmer to induce a labyrinthine vasculature and attenuate SL formation.</p><p><strong>Conclusions: </strong>Our findings provide evidence that downregulating uPARAP expression can induce a beneficial remodeling of lymphatic vasculature that attenuates lymphedema through a cell junction-based mechanism, offering a novel therapeutic pathway for lymphedema.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1412-1429"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539431","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":"Ezh2 Shapes T Cell Plasticity to Drive Atherosclerosis.","authors":"Cecilia Assunta Bonfiglio, Michael Lacy, Vasiliki Triantafyllidou, Floriana Maria Farina, Aleksandar Janjic, Katrin Nitz, Yuting Wu, Venetia Bazioti, Irem Avcilar-Kücükgöze, Yonara Freire Soares Marques, Markus Joppich, Mahadia Kumkum, Katja Röß, Anuroop Venkateswaran Venkatasubramani, Axel Imhof, Wolfgang Enard, Lars Maegdefessel, Menno de Winther, Christian Weber, Donato Santovito, Esther Lutgens, Dorothee Atzler","doi":"10.1161/CIRCULATIONAHA.124.072384","DOIUrl":"10.1161/CIRCULATIONAHA.124.072384","url":null,"abstract":"<p><strong>Background: </strong>The activation and polarization of T cells play a crucial role in atherosclerosis and dictate athero-inflammation. The epigenetic enzyme EZH2 (enhancer of zeste homolog 2) mediates the H3K27me3 (trimethylation of histone H3 lysine 27) and is pivotal in controlling T cell responses.</p><p><strong>Methods: </strong>To detail the role of T cell EZH2 in atherosclerosis, we used human carotid endarterectomy specimens to reveal plaque expression and geography of EZH2. Atherosclerosis-prone <i>Apoe</i> (apolipoprotein E)-deficient mice with CD (cluster of differentiation) 4⁺ or CD8⁺ T cell-specific <i>Ezh2</i> deletion (Ezh2^cd4-knockout [KO], Ezh2^cd8-KO) were analyzed to unravel the role of T cell Ezh2 in atherosclerosis and T cell-associated immune status.</p><p><strong>Results: </strong><i>EZH2</i> expression is elevated in advanced human atherosclerotic plaques and primarily expressed in the T cell nucleus, suggesting the importance of canonical EZH2 function in atherosclerosis. Ezh2^cd4-KO, but not Ezh2^cd8-KO, mice showed reduced atherosclerosis with fewer advanced plaques, which contained less collagen and macrophages, indicating that Ezh2 in CD4⁺ T cells drives atherosclerosis. In-depth analysis of CD4⁺ T cells of Ezh2^cd4-KO mice revealed that absence of Ezh2 results in a type 2 immune response with increased Il-4 (interleukin 4) gene and protein expression in the aorta and lymphoid organs. In vitro, <i>Ezh2</i>-deficient T cells polarized macrophages toward an anti-inflammatory phenotype. Single-cell RNA-sequencing of splenic T cells revealed that <i>Ezh2</i> deficiency reduced naive, Ccl5⁺ (C-C motif chemokine ligand 5) and regulatory T cell populations and increased the frequencies of memory T cells and invariant natural killer T (iNKT) cells. Flow cytometric analysis identified a shift toward Th2 (type 2 T helper) effector CD4⁺ T cells in Ezh2^cd4-KO mice and confirmed a profound increase in splenic iNKT cells with increased expression of Plzf (promyelocytic leukemia zinc finger), which is the characteristic marker of the iNKT2 subset. Likewise, <i>Zbtb16</i> ([zinc finger and BTB domain containing 16], the Plzf-encoding gene) transcripts were elevated in the aorta of Ezh2^cd4-KO mice, suggesting an accumulation of iNKT2 cells in the plaque. H3K27me3-chromatin immunoprecipitation followed by quantitative polymerase chain reaction showed that T cell-Ezh2 regulates the transcription of the <i>Il-4</i> and <i>Zbtb16</i> genes.</p><p><strong>Conclusions: </strong>Our study uncovers the importance of T cell EZH2 in human and mouse atherosclerosis. Inhibition of Ezh2 in CD4⁺ T cells drives type 2 immune responses, resulting in an accumulation of iNKT2 and Th2 cells, memory T cells and anti-inflammatory macrophages that limit the progression of atherosclerosis.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1391-1408"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363799","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":"Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From VALOR-HCM.","authors":"Milind Y Desai, Kathy Wolski, Anjali Owens, Jeffrey B Geske, Sara Saberi, Andrew Wang, Mark Sherrid, Paul C Cremer, Neal K Lakdawala, Albree Tower-Rader, David Fermin, Srihari S Naidu, Nicholas G Smedira, Hartzell Schaff, Zhiqun Gong, Lana Mudarris, Kathy Lampl, Amy J Sehnert, Steven E Nissen","doi":"10.1161/CIRCULATIONAHA.124.072445","DOIUrl":"10.1161/CIRCULATIONAHA.124.072445","url":null,"abstract":"<p><strong>Background: </strong>In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128.</p><p><strong>Methods: </strong>A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128.</p><p><strong>Results: </strong>At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction <50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years).</p><p><strong>Conclusions: </strong>In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04349072.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1378-1390"},"PeriodicalIF":35.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647064","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":"The Association Between Tirzepatide Versus Insulin Glargine and NT-proBNP Levels in People With Type 2 Diabetes With or at Elevated Risk for Cardiovascular Disease: Post hoc Analyses of SURPASS 4.","authors":"Naveed Sattar,Govinda J Weerakkody,Darren K McGuire,Mikhail N Kosiborod,Matthew M Y Lee,Paul Welsh,Ewan R Pearson,Russell J Wiese,Kevin Duffin,Jonathan Wilson,Noemi Pavo,Martin Hülsmann,Imre Pavo","doi":"10.1161/circulationaha.124.072889","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072889","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"209 1","pages":"1430-1432"},"PeriodicalIF":37.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945146","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":"Cell Type-Level Epigenetics at the Frontier of Atherosclerosis Research.","authors":"Anthony S Zannas","doi":"10.1161/circulationaha.125.074275","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074275","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"11 1","pages":"1409-1411"},"PeriodicalIF":37.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945145","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":"Letter by Zhang et al Regarding Article, \"Excess Mortality and Loss of Life Expectancy After Myocardial Infarction: A Registry-Based Matched Cohort Study\".","authors":"Zhiqiang Zhang,Xinyue Yang,Zhiyi Zhang","doi":"10.1161/circulationaha.124.071553","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071553","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"52 1","pages":"e986-e987"},"PeriodicalIF":37.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945144","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":"Response by Reitan et al to Letter Regarding Article, \"Excess Mortality and Loss of Life Expectancy After Myocardial Infarction: A Registry-Based Matched Cohort Study\".","authors":"Christian Reitan,Pontus Andell,Robin Hofmann,Tomas Jernberg","doi":"10.1161/circulationaha.125.073963","DOIUrl":"https://doi.org/10.1161/circulationaha.125.073963","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"35 1","pages":"e988-e989"},"PeriodicalIF":37.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945143","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}