Circulation最新文献

{"title":"Treatment Response to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy: 96-Week Results From the EXPLORER Cohort of the MAVA-Long-Term Extension Cardiac Magnetic Resonance Imaging Substudy.","authors":"Sara Saberi,Christopher M Kramer,Artur Oręziak,Ahmad Masri,Roberto Barriales-Villa,Theodore P Abraham,Neal K Lakdawala,Andrew Wang,Lubna Choudhury,Florian Rader,Ofer Havakuk,John C Stendahl,Nuno Cardim,Tim Seidler,Mark Sherrid,Sheila M Hegde,Raymond Y Kwong,Michael Jerosch-Herold,Ganesh Balaratnam,Gregory Kurio,Shawna Fox,Iacopo Olivotto,Anjali Owens","doi":"10.1161/circulationaha.124.071188","DOIUrl":"https://doi.org/10.1161/circulationaha.124.071188","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"41 1","pages":"905-908"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117137","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":"The Association of Time to Reperfusion With VA-ECMO With Survival of Patients Who Experience Refractory Out-of-Hospital Cardiac Arrest.","authors":"Marinos Kosmopoulos,Despoina Koukousaki,Eleanna Yannopoulou,Pierre Spaulding Sebastian,Christopher Erik Monti,Rajat Kalra,Aaron Burnett,Charles Bruen,Peter Tanghe,Bjorn Peterson,Tamas Alexy,Jason Alan Bartos,Sergey Gurevich,Ganesh Raveendran,Henry Halperin,Tom Paul Aufderheide,Demetris Yannopoulos","doi":"10.1161/circulationaha.125.074507","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074507","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"80 1","pages":"902-904"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117136","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 Zhong et al Regarding Article, \"Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS\".","authors":"Yumei Zhong,Rui Lai,Xinmin Deng","doi":"10.1161/circulationaha.124.073672","DOIUrl":"https://doi.org/10.1161/circulationaha.124.073672","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"10 1","pages":"e241-e242"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117133","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":"Role of A2AR-D2R Dimerization and D2R-Biased Signaling in PDE10A-Mediated Cardiac Hypertrophy.","authors":"Si Chen,Xinyue Fan,Sumin Xu,Nichen Zhu,Hangchuan Shi,Zheng-Gen Jin,Chen Yan","doi":"10.1161/circulationaha.125.075465","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075465","url":null,"abstract":"BACKGROUNDPathological cardiomyocyte (CM) hypertrophy is a hallmark of dilated cardiomyopathy and heart failure, driven by mechanical or neurohumoral stress. Although we previously demonstrated PDE10A (phosphodiesterase 10A) as a critical contributor and potential therapeutic target in pathological cardiac remodeling and dysfunction, the underlying mechanisms remain unclear. Here, we investigated the specific signaling pathways and sources of cyclic nucleotides modulated by PDE10A in CM hypertrophy.METHODSCM hypertrophy was induced by angiotensin II in isolated adult mouse CMs, with hypertrophy assessed by cell surface area and protein synthesis. PDE10A inactivation was achieved through PDE10A knockout or inhibition with TP-10. Various pharmacological agonists/antagonists, genetic mutants, and knockout models of D2R (dopamine receptor D2) and A2AR (adenosine receptor 2A) were used to study the role of A2AR-D2R heterodimer and downstream signaling in CM hypertrophy in vitro and in vivo. Viral vectors were used to manipulate protein or shRNA expression targeting key signaling molecules.RESULTSWe demonstrated that the antihypertrophic effect of PDE10A inactivation is specifically dependent on cAMP/PKA (protein kinase A) signaling. Importantly, we discovered an A2AR-D2R heterodimer and its association with PDE10A in CMs. The A2AR-D2R heterodimer mediates the βarr2 (beta-arrestin 2)-biased D2R signaling, and activating D2R-biased signaling antagonizes cardiac hypertrophy and dysfunction. PDE10A deficiency or inhibition enhanced A2AR-D2R heterodimerization, promoting βarr2-biased D2R signaling and downstream PP2A (protein phosphatase 2A)-B56δ activation through increased A2AR/cAMP/PKA-mediated D2R phosphorylation. PDE10A inactivation inhibits stress signal-induced HDAC5 (histone deacetylase 5) nuclear export and phosphorylation, which are dependent on PP2A. Genetic and pharmacological approaches in animal models confirmed the critical roles of A2AR-D2R heterodimerization, D2R phosphorylation, and biased D2R signaling in vivo. Furthermore, combining PDE10A inhibition with A2AR or D2R-biased agonism produced synergistic antihypertrophic effects, highlighting their novel therapeutic potential.CONCLUSIONSOur findings reveal A2AR-D2R dimerization and βarr2-biased D2R signaling as novel and critical mechanisms for counteracting pathological CM hypertrophy and cardiac dysfunction. PDE10A acts as a pivotal negative regulator of this signaling axis. Targeting PDE10A, A2AR-D2R/βarr2 signaling, or both offers potentially novel therapeutic strategies for combating pathological cardiac remodeling and cardiac dysfunction.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"79 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083492","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":"Fibroblast-Specific Loss of TGF-β Signaling Mediates Lipomatous Metaplasia in the Infarcted Heart.","authors":"Izabela Tuleta,Harikrishnan Venugopal,Kevin O'Leary,Deyou Zheng,Nikolaos G Frangogiannis","doi":"10.1161/circulationaha.125.075676","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075676","url":null,"abstract":"BACKGROUNDIn patients surviving myocardial infarction, adipose tissue infiltration within the scar is a common pathological finding and has been suggested to contribute to dysfunction and arrhythmogenesis. However, the cellular mechanisms for lipomatous metaplasia after infarction remain enigmatic. Our study reveals a novel molecular mechanism that mediates fibroblast-to-adipocyte conversion and causes fatty infiltration in the infarcted heart.METHODSMice with fibroblast-specific disruption of TGF-β (transforming growth factor β) or Smad-dependent signaling and corresponding controls were generated and underwent reperfusion and nonreperfusion myocardial infarction protocols. Echocardiography, histological studies, and transcriptomic analysis were used to study effects on cardiac repair and remodeling. Lineage tracing experiments were used to document fibroblast-to-adipocyte conversion. In vitro, the effects of genetic disruption or pharmacological blockade of TGF-β signaling on mouse cardiac fibroblasts were examined. Single-cell RNA sequencing data from human patients with myocardial infarction were analyzed to assess fibroblast-to-adipocyte conversion.RESULTSFibroblast-specific abrogation of TGF-β signaling through deletion of TbR2 (type 2 TGF-β receptor) increased the incidence of early postinfarction cardiac rupture, promoting a matrix-degrading fibroblast phenotype. Moreover, fibroblast-specific TbR2 loss resulted in replacement of 30% to 40% of the mature scar with adipocytes in both reperfused and nonreperfused infarcts. Lineage tracing demonstrated that fibroblast-specific TbR2 loss promotes fibroblast-to-adipocyte conversion through effects that involve Smad-independent cascades. In vitro, TbR2 inhibition induced expression of adipogenesis-associated genes in primary cardiac fibroblasts. Genetic TbR2 loss promoted conversion of infarct fibroblasts to adipocytes upon stimulation with adipogenic medium. A subpopulation of fibroblasts in human fibrotic infarcted hearts acquired expression of adipocyte genes.CONCLUSIONSTGF-β signaling plays a central role in maintaining fibroblast cell specification after cardiac injury. Fibroblast-to-adipocyte conversion induced by disrupted TGF-β signaling may underlie scar-associated lipomatous metaplasia and may play an important role in the pathogenesis of heart failure and arrhythmogenesis in patients with ischemic cardiomyopathy.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"28 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083491","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":"TAX1BP3 Is a SUMOylated Nucleocytoplasmic Shuttling Protein and Protects Against Vascular Neointimal Hyperplasia.","authors":"Hanyan Yang,Yulong Zhong,Wenjie Guo,Wenjing Guo,Boliang Chen,Zexuan Lin,Qin Zhang,Rongjun Zou,Xiaolong Cao,Fengxian Li,Wei Feng,Jianyun Yan,Zhi Zeng,Wei Wang,Kunfu Ouyang,Xinjie Xu,Xiaoping Fan,Xi Fang,Shanshan Ai,Canzhao Liu","doi":"10.1161/circulationaha.124.072525","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072525","url":null,"abstract":"BACKGROUNDNeointimal hyperplasia is the major cause of significant vascular complications after arterial interventions. Despite the advancements in strategies such as drug-eluting stents to minimize neointimal hyperplasia, achieving consistently effective long-term outcomes remains a challenge. Protein-protein interactions mediated by PDZ (PSD-95, Discs-large, and ZO-1) domains are essential for numerous biological processes. However, little is known about the role of PDZ proteins in neointima formation. This study aims to explore the role of TAX1BP3 (Tax1 binding protein 3), a singular PDZ protein, in phenotypic switching of vascular smooth muscle cells (VSMCs) and its implication in neointimal hyperplasia.METHODSSubcellular localization of TAX1BP3 was assessed in isolated VSMCs or arteries obtained from mice with neointima formation. TAX1BP3 mutants were constructed to study the role of SUMOylation on TAX1BP3 nucleocytoplasmic shuttling. VSMC-specific Tax1bp3 knockout mice were generated to determine the relevant phenotypes in a carotid artery wire injury model. RNA sequencing, assays for transposase-accessible chromatin using sequencing, computational prediction of complex structures, and coimmunoprecipitation were performed to elucidate the underlying molecular mechanisms. AAV-mediated Tax1bp3 gene delivery and engineered AIENP-TAX1BP3 were employed to investigate the potential translational relevance.RESULTSTAX1BP3 exhibited dynamic nucleocytoplasmic shuttling during phenotypic switching of VSMCs. TAX1BP3 is SUMOylated at K116, and its SUMOylation is essential for maintaining the nuclear localization of TAX1BP3. Deficiency of TAX1BP3 facilitated the transition from a contractile to a synthetic phenotype and aggravated neointima formation after vascular injury in mice. The integration of RNA sequencing and an assay for transposase-accessible chromatin using sequencing unveiled that TAX1BP3 primarily regulated the cell cycle progression and cell proliferation of VSMCs through YAP-TEAD transcription activity. The computational prediction of TAX1BP3/YAP1 complex structures and protein interaction-related experiments revealed that TAX1BP3 and TEAD1 compete for binding to YAP through its TEAD binding domain (BD) in a noncanonical PDZ manner. AAV-mediated Tax1bp3 gene delivery significantly attenuated postinjury neointima formation and the progression of atherosclerosis. AIENP-TAX1BP3 administration effectively reduced VSMC phenotypic switching and neointimal hyperplasia.CONCLUSIONSThese results demonstrate that SUMOylation of TAX1BP3 at K116 enables its nucleocytoplasmic shuttling during phenotypic switching of VSMCs. TAX1BP3 competitively interacts with the YAP-TEAD complex in a noncanonical PDZ manner and exerts its protective role in vascular neointimal hyperplasia primarily through the regulation of cell proliferation.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"38 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068355","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":"Use of Risk Assessment to Guide Decision-Making for Blood Pressure Management in the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology.","authors":"Sadiya S Khan, Marwah Abdalla, Natalie A Bello, Ciantel A Blyler, Jocelyn Carter, Yvonne Commodore-Mensah, Keith C Ferdinand, Heather M Johnson, Daniel Jones, Amit Khera, Paul Muntner, Stacey Schott, Daichi Shimbo, Sidney C Smith, Sandra J Taler, Eugene Yang, Donald M Lloyd-Jones","doi":"10.1161/CIR.0000000000001355","DOIUrl":"10.1161/CIR.0000000000001355","url":null,"abstract":"<p><p>Risk assessment plays a central role in the primary prevention of cardiovascular disease. The 2017 High Blood Pressure Clinical Practice Guideline incorporated quantitative risk assessment for the first time to guide the initiation of antihypertensive drug therapy and recommended calculation of 10-year risk of atherosclerotic cardiovascular disease with the Pooled Cohort Equations. Although the 2025 High Blood Pressure Guideline reaffirmed this overarching paradigm for risk-based initiation of antihypertensive drug therapy, it updated the recommended risk model to the Predicting Risk of Cardiovascular Disease Events equations, which estimate 10-year risk of total cardiovascular disease (including atherosclerotic cardiovascular disease and heart failure), and defined a new risk threshold for initiation of antihypertensive therapy in patients with stage 1 hypertension. This American Heart Association/American College of Cardiology scientific statement summarizes the rationale to recommend the use of the Predicting Risk of Cardiovascular Disease Events equations, the evidence base for the new threshold of 10-year risk of cardiovascular disease of ≥7.5%, and the population-level implications of these revised recommendations. This scientific statement also offers practical advice for implementing risk assessment as the first step in the comprehensive approach to hypertension management with shared decision-making between patients and clinicians. Remaining gaps in awareness and treatment of hypertension underscore the need for innovative strategies to improve implementation of and adherence to risk-based guideline recommendations, including automation of risk assessment in electronic health records, decision-support aids, and refinement of risk assessment, to equitably improve the initiation of antihypertensive drug therapy, blood pressure control, and outcomes.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"e219-e238"},"PeriodicalIF":38.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945273","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":"Decoding Supraventricular Tachycardia by Holter ECG Analysis.","authors":"Mustafa Gabarin,Syamkumar Divakara Menon","doi":"10.1161/circulationaha.125.075207","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075207","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"10 1","pages":"836-839"},"PeriodicalIF":37.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068362","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":"Intensity, Duration, and Context Dependency of the Responses to Nutrient Surplus and Deprivation Signaling in the Heart: Insights Into the Complexities of Cardioprotection.","authors":"Milton Packer","doi":"10.1161/circulationaha.125.075568","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075568","url":null,"abstract":"Nutrient surplus sensing through PI3K (phosphoinositide-3-kinase) and mTOR (mechanistic target of rapamycin) stimulates anabolism to expand cellular mass, whereas nutrient and energy deprivation sensing through SIRT1 (sirtuin-1) and AMPK (adenosine monophosphate-activated protein kinase) promotes catabolism to support cytoprotective quiescence. By signaling through downstream effectors (PGC-1α [peroxisome proliferator-activated receptor gamma coactivator 1-alpha], PPARα/PPARγ, FoxO1 [forkhead box protein family O1], NRF2 [nuclear factor erythroid-derived factor 2], HIF-1α [hypoxia-inducible factor-1α], and HO-1 [heme oxygenase-1]), environmental nutrients, growth factors, and cellular stress influence mitochondrial biogenesis, autophagic flux, cardiac hypertrophy, and cardiomyocyte senescence and apoptosis. Despite these canonical descriptions, the actual response to each effector is determined by the intensity and duration of signaling. Typically, transient and measured signaling produces adaptive effects, whereas continuous heightened activity yields maladaptive responses. The effects of signaling are also influenced by context; ie, the nature and intermittency of the external stress and the characteristics of the underlying substrate (eg, cardiomyopathy, obesity, or aging). PI3K signaling promotes physiological hypertrophy and is cardioprotective during abrupt cardiac stress, but its sustained activation accelerates pathological hypertrophy related to obesity and aging. Signaling through SIRT1/AMPK (and upregulation of autophagic flux) exerts favorable effects during exercise training and in chronic cardiomyopathy, obesity, and aging, but it undermines the cardiac response to abrupt stress. Intermittent FoxO1 upregulation may promote physiological hypertrophy while antagonizing pathological hypertrophy, but prolonged activation leads to cardiomyocyte apoptosis. NRF2 exerts antioxidant effects when background autophagic flux is vigorous but aggravates cellular stress when autophagy is suppressed (as in pathological hypertrophy). Sustained activation of PPARγ, NRF2, and HIF-1α in nutrient surplus states can lead to maladaptive ventricular remodeling, thus explaining the results of clinical trials with thiazolidinediones, bardoxolone, and prolyl hydroxylase inhibitors. The influence of duration, intensity, and context may be mediated (in part) by the activation or suppression of counterregulatory mechanisms, by the selective recruitment of corepressors, and by posttranslational protein modifications. These observations, considered collectively, suggest that no protein or cellular process viewed in isolation can be regarded as cardioprotective or maladaptive. Cell signals operate usefully if they are delivered as part of an orchestrated program of compartmentalized nuanced bursts, acting as elements of multifaceted oscillating systems whose periodicity is determined by the need to achieve homeostasis.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"72 1","pages":"802-835"},"PeriodicalIF":37.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068384","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-Course Secondary Antibiotic Prophylaxis for Children With Screen-Detected Mild Rheumatic Heart Disease.","authors":"Joselyn Rwebembera,Craig Sable,Anneke C Grobler,Jafesi Pulle,Amy Scheel,Mucunguzi Atukunda,Alison M Spaziani,Daniel Engelman,Jonathan Carapetis,Ganesan Karthikeyan,Peter Lwabi,Liesl Zühlke,Maria C P Nunes,Nigel Wilson,Ana Olga Mocumbi,Emma Ndagire,Christine Mwaka Okwera,Susan Akullo,Julious Etyang,Alannah Rudkin,Rachel Sarnacki,Miriam Nakitto,Brenda Atim,Emmy Okello,Andrew Steer,Andrea Beaton","doi":"10.1161/circulationaha.125.074969","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074969","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"15 1","pages":"840-842"},"PeriodicalIF":37.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068361","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}