Circulation最新文献

{"title":"Hypertriglyceridemia as a Key Contributor to Abdominal Aortic Aneurysm Development and Rupture: Insights From Genetic and Experimental Models.","authors":"Yaozhong Liu, Huilun Wang, Minzhi Yu, Lei Cai, Ying Zhao, Yalun Cheng, Yongjie Deng, Yang Zhao, Haocheng Lu, Xiaokang Wu, Guizhen Zhao, Chao Xue, Hongyu Liu, Ida Surakka, Anna Schwendeman, Hong S Lu, Alan Daugherty, Lin Chang, Jifeng Zhang, Ryan E Temel, Y Eugene Chen, Yanhong Guo","doi":"10.1161/CIRCULATIONAHA.125.074737","DOIUrl":"10.1161/CIRCULATIONAHA.125.074737","url":null,"abstract":"<p><strong>Background: </strong>Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with no effective pharmacological treatments. The causal role of triglycerides (TGs) in AAA development remains unclear and controversial.</p><p><strong>Methods: </strong>Mendelian randomization was applied to assess causal relationships between lipoproteins, circulating proteins, metabolites, and the risk of AAA. To test the hypothesis that elevated plasma TG levels accelerate AAA development, we used <i>Lpl</i>-deficient, <i>Apoa5</i>-deficient, and human <i>APOC3</i> transgenic mice, which display varying degrees of hypertriglyceridemia. Mechanistic studies were performed using RNA sequencing and Western blot analysis of palmitate-treated vascular smooth muscle cells and validated in vivo by local overexpression of key mediator in the suprarenal abdominal aorta. Antisense oligonucleotides targeting <i>Angptl3</i> were administered to reduce TG levels and assess therapeutic potential in human <i>APOC3</i> transgenic and <i>Apoe</i>-deficient mice.</p><p><strong>Results: </strong>Mendelian randomization analyses integrating genetic, proteomic, and metabolomic data identified causal relationships between elevated TG-rich lipoproteins, TG metabolism-related proteins/metabolites, and AAA risk. In the angiotensin II infusion AAA model, most <i>Lpl</i>-deficient mice with severely elevated TG concentrations died of aortic rupture. Similarly, <i>Apoa5</i>-deficient mice with moderately elevated TG levels developed accelerated AAA, and human <i>APOC3</i> transgenic mice with dramatically elevated TG levels exhibited aortic dissection and rupture. Mechanistically, elevated TG and palmitate inhibited lysyl oxidase (LOX) maturation and reduced LOX activity. Locally overexpressing lysyl oxidase eliminated the proaneurysmal effect of hypertriglyceridemia in human <i>APOC3</i> transgenic mice. Moreover, an <i>Angptl3</i>-targeting antisense oligonucleotide profoundly attenuated AAA progression in both human <i>APOC3</i> transgenic and <i>Apoe</i>-deficient mice.</p><p><strong>Conclusions: </strong>These findings identify hypertriglyceridemia as a key contributor to AAA pathogenesis and suggest that targeting TG-rich lipoproteins may be a promising therapeutic strategy for AAA.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"862-881"},"PeriodicalIF":38.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12327802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783636","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":"Letter by Feng 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":"Suyin Feng,Ziheng Wang,Runfeng Sun","doi":"10.1161/circulationaha.124.073382","DOIUrl":"https://doi.org/10.1161/circulationaha.124.073382","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"52 1","pages":"e239-e240"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117138","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":"Mechanism Behind QRS Widening With Faster Pacing.","authors":"Cameron M Cupp,Ignatius Gerardo E Zarraga","doi":"10.1161/circulationaha.125.076354","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076354","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"11 1","pages":"899-901"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117139","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 Ji et al to Letters Regarding Article, \"Association of Coagulation Factor XI Level With Cardiovascular Events and Cardiac Function in Community-Dwelling Adults: From ARIC and CHS\".","authors":"Yuekai Ji,Lin Yee Chen,Michael J Zhang","doi":"10.1161/circulationaha.125.075646","DOIUrl":"https://doi.org/10.1161/circulationaha.125.075646","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"16 1","pages":"e243-e244"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117135","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 Persistent Family Feud: CABG Versus PCI. Do We Even Need a Winner?","authors":"Rasha Al-Lamee,Shayna Chotai","doi":"10.1161/circulationaha.125.074726","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074726","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"30 1","pages":"859-861"},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117141","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":"Post-Myocardial Infarction Psychological Distress: A Scientific Statement From the American Heart Association.","authors":"Glenn N Levine,Robert M Carney,Beth E Cohen,Susan L Dunn,Allison E Gaffey,Ian M Kronish,Erik M G Olsson,Jeff C Huffman, ","doi":"10.1161/cir.0000000000001381","DOIUrl":"https://doi.org/10.1161/cir.0000000000001381","url":null,"abstract":"The importance of psychological distress in patients with cardiovascular disease is increasingly recognized as both a contributing factor to the development and progression of cardiovascular disease and a consequence of the development of cardiovascular disease. Patients with acute myocardial infarction have increased risks for depression, anxiety, psychosocial stress, or posttraumatic stress disorder. Together, these negative psychological factors when occurring after myocardial infarction have been referred to as postmyocardial psychological distress. Up to half of patients after myocardial infarction may experience some form of psychological distress, and this postmyocardial psychological distress has been associated with an increased risk of future cardiac events. Biologically plausible mechanisms by which postmyocardial psychological distress may lead to increased future cardiac risk include lesser physical activity, smoking (and failure to stop smoking), excess alcohol consumption, poor diet, obesity, inadequate sleep, inadequate social support, decreased medication adherence, and poor attendance at cardiac rehabilitation. The data on whether treatment of postmyocardial psychological distress improves cardiac prognosis are mixed and of variable quality, and further studies, particularly in patients with anxiety, stress, and posttraumatic stress disorder, would be helpful. Regardless, multiple interventions can reduce psychological distress and thus lead to improved psychological health, a greater sense of emotional well-being, and a better quality of life. A goal of health care professionals should be to treat not only the disease but also the person as a whole in front of us.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"1 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103391","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":"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}