Circulation research最新文献

{"title":"Cutting Loose to Hold on: A Feedback Loop Between GPLD1 and uPAR in Heart Failure.","authors":"Julia Palacios-Merino,Enrique Lara-Pezzi","doi":"10.1161/circresaha.125.327057","DOIUrl":"https://doi.org/10.1161/circresaha.125.327057","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"750 1","pages":"584-586"},"PeriodicalIF":20.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850886","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":"Obstructive Sleep Apnea and Cardiometabolic Disease: Obesity, Hypertension, and Diabetes.","authors":"Esra Tasali,Sushmita Pamidi,Naima Covassin,Virend K Somers","doi":"10.1161/circresaha.125.325676","DOIUrl":"https://doi.org/10.1161/circresaha.125.325676","url":null,"abstract":"Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, characterized by recurrent upper airway obstruction during sleep, resulting in intermittent hypoxia, increased sympathetic activation, and sleep deficiency. Over the past 2 decades, there has been a robust body of evidence to support a strong link between OSA and cardiometabolic diseases. Obesity is an important risk factor for OSA. Observational studies indicate that OSA is a strong risk factor for the development of hypertension and diabetes. Moreover, clinical and experimental studies support a causal role of OSA in hypertension and impairments in glucose metabolism, beyond excess weight. Notably, OSA is particularly underdiagnosed and undertreated in women, which may heighten the cardiometabolic risk. OSA is often overlooked during pregnancy and has been linked to adverse cardiometabolic outcomes in observational studies. In randomized clinical trials, treatment of OSA with continuous positive airway pressure reduces blood pressure in individuals with hypertension, but the beneficial effects of continuous positive airway pressure on glycemic outcomes are less convincing. Inconsistent cardiometabolic response to OSA treatment can be partly explained by failure to consider heterogeneity in OSA and variable continuous positive airway pressure adherence among diverse populations. In this review, we summarize the relationships between OSA and cardiometabolic conditions with a particular focus on obesity, hypertension, and diabetes. We review the current knowledge on the heterogeneity in OSA and discuss potential underlying mechanisms for impairments in blood pressure and glucose metabolism in OSA. We also provide a clinical perspective for OSA management considering current research gaps and emerging approaches for the prevention and treatment of cardiometabolic disease.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"272 1","pages":"764-787"},"PeriodicalIF":20.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850899","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":"Sleep and Cardiovascular Health: An Introduction to the Series.","authors":"Susan Redline","doi":"10.1161/circresaha.125.327119","DOIUrl":"https://doi.org/10.1161/circresaha.125.327119","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"70 1","pages":"705-708"},"PeriodicalIF":20.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851247","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":"Sleep Disruption and Atrial Fibrillation: Evidence, Mechanisms and Clinical Implications.","authors":"Abhishek Deshmukh,Naima Covassin,Yves Dauvilliers,Virend K Somers","doi":"10.1161/circresaha.125.325612","DOIUrl":"https://doi.org/10.1161/circresaha.125.325612","url":null,"abstract":"Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, with its incidence rising due to aging populations, obesity, and advancements in diagnostic modalities. The interplay between sleep disorders and AF is increasingly recognized, with obstructive sleep apnea (OSA) serving as a well-established risk factor. However, emerging evidence implicates additional sleep disturbances-including central sleep apnea, insomnia, and restless legs syndrome-in AF pathogenesis and progression. Despite compelling observational data, interventional studies evaluating the impact of sleep disorder treatment on AF outcomes have yielded mixed results. Although continuous positive airway pressure therapy in patients with OSA mitigates AF recurrence, randomized controlled trials have yet to confirm a definitive causal benefit. This review synthesizes epidemiological, mechanistic, and interventional data linking sleep disorders to AF.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"8 1","pages":"788-808"},"PeriodicalIF":20.1,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850887","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":"Dicer Neosynthesis Regulates Platelet Reactivity: A Mechanism Altered in Type 2 Diabetes.","authors":"Loredana Bury,Elisa Piselli,Giorgia Manni,Stefania Momi,Giulia Ciarrocca Taranta,Giuseppe Guglielmini,Carmine Fanelli,Michelantonio De Fano,Jesse W Rowley,Andrew S Weyrich,Paolo Gresele","doi":"10.1161/circresaha.124.325357","DOIUrl":"https://doi.org/10.1161/circresaha.124.325357","url":null,"abstract":"RATIONALEDespite being anucleate, platelets contain mRNAs and synthesize new proteins. Platelets also contain microRNAs and Dicer, an enzyme required for microRNA maturation. The expression of Dicer and some microRNAs is reduced in platelets from patients with type 2 diabetes (T2DM). However, the role of Dicer in the regulation of platelet function and in T2DM-associated platelet hyperreactivity is unclear.OBJECTIVEWe aimed to assess whether Dicer levels are regulated in platelets upon activation, if they modulate mRNA translation by triggering pre-microRNA maturation, and whether these mechanisms are deranged in T2DM platelets.METHODS AND RESULTSDicer expression was assessed by Western blotting, flow cytometry, and liquid chromatography-tandem mass spectrometry. The P2Y12 expression was assessed by Western blotting and microRNA-223 and P2RY12 (purinergic receptor P2Y12) transcript by real-time polymerase chain reaction. In vivo experiments were performed in Dicer-deficient and wild-type mice with alloxane-induced diabetes. Thrombin-activated platelets from healthy individuals rapidly neosynthesize Dicer, leading to increased maturation of microRNA-223 levels and concomitant consumption of pre-microRNA-223. An increase in microRNA-223 was associated with a reduction of P2RY12 mRNA, one of its main targets, and platelet P2Y12 expression and function. All these mechanisms were significantly deranged in platelets from patients with T2DM. Similar alterations were also observed in platelets from Dicer-deficient and diabetic mice. The Dicer-triggered decrease in P2Y12 after thrombin stimulation may represent a self-regulatory mechanism of platelet activation to prevent undesired thrombus formation, as shown by lower ADP-induced platelet pulmonary thromboembolism in mice previously infused with low-dose thrombin. The derangement of this self-regulatory mechanism in T2DM may contribute to the platelet hyperreactivity and enhanced thrombotic complications of patients with T2DM.CONCLUSIONSOur results show that the complex regulatory role of microRNA neoformation during platelet activation, when deranged, may contribute to cardiovascular disease.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"30 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778094","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":"Myeloid-Specific STING-YBX1 Interaction Alleviates Coagulation in Deep Vein Thrombosis.","authors":"Zhiye Guo,Xiaolong Du,Chunlei Xing,Zhiguang Shi,Dandan Xu,Feng Ran,Li Su,Shan Lu","doi":"10.1161/circresaha.125.326540","DOIUrl":"https://doi.org/10.1161/circresaha.125.326540","url":null,"abstract":"BACKGROUNDDeep vein thrombosis (DVT), the third most common cause of cardiovascular deaths, is characterized by intravascular clot formation, often accompanied by inflammation. Although the STING (stimulator of interferon genes) signaling pathway is well recognized for its role in mediating inflammation in the context of infection, cellular stress, and tissue, its intricate involvement in DVT remains enigmatic.METHODSIn this study, we investigated the role of myeloid cell-intrinsic STING signaling in DVT progression using murine models. Both STING inhibitors and genetic depletion of myeloid-specific STING were used to assess their effects on thrombus formation. In addition, we explored the interaction between STING and YBX1 (Y-box-binding protein 1) through biochemical analyses. A synthetic peptide, C-ST16, designed to mimic STING inhibitors, was tested for its therapeutic potential in reducing thrombus formation and inflammatory responses.RESULTSOur results demonstrate that myeloid cell-intrinsic STING signaling is a key driver in DVT progression. STING inhibition, either through specific inhibitors or genetic depletion of myeloid-specific STING, significantly ameliorated thrombus formation in murine DVT models. Furthermore, we identified a direct interaction between STING and YBX1, resulting in nuclear translocation and heightened thrombotic inflammation. The synthetic peptide, C-ST16, effectively reduced thrombus formation and inflammatory factor expression, without causing hepatorenal toxicity.CONCLUSIONSThese findings highlight the critical role of myeloid-specific STING-YBX1 signaling in driving inflammation during DVT progression. The potential therapeutic use of STING inhibitors, particularly the synthetic peptide C-ST16, presents a promising approach for DVT management, offering novel insights into targeted anti-inflammatory therapies for thrombotic disorders.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"100 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778092","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":"CAR Macrophages Engineered In Vivo for Attenuating Myocardial Ischemia-Reperfusion Injury.","authors":"Heng Du,Xintong You,Jiahe Zhang,Siqi Liu,Yanan Zhou,Yuhan Wang,Chaofan Yang,Yanan Meng,Xu Liu,Hao Zhang,Yujing Li,Jianghua Shen,Hailong Yuan,Pengfei Xu,Chuting He,Yi Xiao,Zeyu Gao,Jingyi Zang,Tuo Wei,Moshi Song","doi":"10.1161/circresaha.125.326716","DOIUrl":"https://doi.org/10.1161/circresaha.125.326716","url":null,"abstract":"BACKGROUNDMyocardial ischemia-reperfusion (I/R) injury induces myocardial fibrosis that compromises cardiac function and electrical conduction, yet current clinical options remain inadequate. To address this unmet need, we explored macrophage-targeted lipid nanoparticles (LNPs) encapsulating FAP CAR (FAP [fibroblast activation protein]-targeted chimeric antigen receptor) mRNA for in vivo generation of FAP CAR macrophages and evaluated their therapeutic potential in reducing myocardial fibrosis and improving cardiac function after myocardial I/R injury.METHODSWe formulated 1,2-dioleoyl-sn-glycero-3-phospho-l-serine-doping ALC-0315 (an ionizable lipid) LNP to deliver FAP CAR mRNA to generate FAP CAR macrophages. The platform was first validated in vitro by assessing phagocytosis of FAP-overexpressing fibroblasts by these macrophages. For in vivo evaluation, C57BL/6J mice subjected to I/R injury received intravenous administration of PBS, control LNPs, or LNP-FAP CAR (LNPs encapsulating mRNA encoding a FAP-targeting CAR). Comprehensive analyses included tracking the biodistribution of the resultant FAP CAR macrophages, quantitative measurement of fibrosis reduction, assessment of cardiac function by echocardiography, and safety evaluations.RESULTSLNP-FAP CAR successfully generated functional FAP CAR macrophages that demonstrated phagocytosis ability toward FAP-positive fibroblasts in vitro. In vivo studies revealed that intravenous delivery of LNP-FAP CAR generated functional FAP CAR macrophages that selectively engaged and phagocytosed activated cardiac fibroblasts in I/R mouse hearts. This targeted cell clearance translated to a significant reduction in the number of activated cardiac fibroblasts and the extent of myocardial fibrosis, as well as marked improvement in cardiac function without detectable toxicities. Notably, these effects were achievable even when intervention was delayed for up to 2 weeks post-I/R.CONCLUSIONSOur study demonstrates that FAP CAR macrophages generated in vivo by LNP-FAP CAR treatment effectively mitigate cardiac fibrosis and improve heart function after I/R injury, with lasting benefits and no observed toxicity. This safe and adaptable platform offers a promising treatment strategy for myocardial I/R injury and holds potential for treating other fibrotic heart diseases.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"29 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778093","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":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000727","DOIUrl":"https://doi.org/10.1161/RES.0000000000000727","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 4","pages":"453-455"},"PeriodicalIF":16.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759299","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":"Sometimes Smaller Is Better.","authors":"William F Jackson","doi":"10.1161/CIRCRESAHA.125.326942","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.125.326942","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"137 4","pages":"471-473"},"PeriodicalIF":16.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759300","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":"BacNav Gene Therapy Improves Function of Infarcted Engineered Human Myocardium and NHPs.","authors":"Tianyu Wu,Nicole G Z Tee,Yiu Yan Siu,Anna Tornatore,Abhishek Bhattacharjee,James Koconis,Szejie Loo,Liping Su,Binjie Li,Lei Ye,Nenad Bursac","doi":"10.1161/circresaha.125.326570","DOIUrl":"https://doi.org/10.1161/circresaha.125.326570","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"14 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756093","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}