Circulation最新文献

{"title":"Insulin Resistance Compromises the Pentose Phosphate Pathway and Impairs Left Ventricular Assist Device-Mediated Myocardial Recovery in Obese Patients With Heart Failure.","authors":"Tuo Pan, Tianyu Liu, Chenyu Jiang, Xiafeng Yu, Yuxi Ji, Jian Liu, Yi Shen, Xingliang Zhou, Yi Yan, Bei Feng, Li Xiang, Erjun Zhu, Qiang Wang, Baowei Shao, Dihao Pan, Liang Ma, Xiangyang Xu, Yanjun Sun, Lin Han, Dongjin Wang, Yiwei Liu, Hao Zhang","doi":"10.1161/CIRCULATIONAHA.124.072850","DOIUrl":"10.1161/CIRCULATIONAHA.124.072850","url":null,"abstract":"<p><strong>Background: </strong>End-stage heart failure (HF) remains a major global health challenge, and left ventricular assist devices (LVADs) represent an important therapeutic option. LVAD-mediated mechanical unloading improves cardiac function and promotes myocardial recovery in many patients with HF; however, this recovery response is suboptimal in obese patients. The mechanisms by which LVAD-mediated unloading induces myocardial recovery, and how obesity alters these processes to blunt myocardial recovery, remain poorly understood.</p><p><strong>Methods: </strong>Patients with HF receiving LVAD support were recruited to investigate the correlation between patients' body mass index and the myocardial recovery response following LVAD implantation. In parallel, a mouse model of heterotopic cervical heart transplantation was used to simulate LVAD-mediated cardiac unloading. Single-nucleus RNA sequencing and stable-isotope tracing metabolomics were performed to explore the changes of signaling pathways and metabolic processes in unloaded hearts. In vitro cyclic stretch assays were used to evaluate how reduced mechanical load regulates cardiomyocyte metabolic pathways. Unloaded hearts from HF mice were used to determine whether the identified metabolic processes contribute to unloading-induced myocardial recovery. Furthermore, the unloaded hearts from obese HF mice were used to evaluate whether these metabolic adaptations are attenuated by obesity.</p><p><strong>Results: </strong>HF patients with a higher body mass index (≥28.0) and greater insulin resistance tended to have poorer LVAD-mediated myocardial recovery. Single-nucleus RNA sequencing showed that mechanical unloading activated myocardial insulin signaling and increased glucose uptake. Stable-isotope tracing metabolomics further revealed that glucose taken up by unloaded hearts was preferentially shunted into the pentose phosphate pathway. Mechanistically, reduced mechanical stress attenuated Hippo pathway activation in cardiomyocytes, facilitating insulin signaling and enhancing pentose phosphate pathway flux. In unloaded hearts from HF mice, increased pentose phosphate pathway flux could reduce oxidative stress and exert cardioprotective effects. However, these benefits were blunted by insulin resistance in obese mice, whereas treatment with insulin sensitizers alleviated insulin resistance and restored unloading-mediated cardioprotection.</p><p><strong>Conclusions: </strong>In failing hearts, mechanical unloading leads to activation of insulin signaling, resulting in increased glucose uptake and enhanced pentose phosphate pathway flux to protect cardiomyocytes against oxidative stress. However, this cardioprotective effect is attenuated by obesity-induced insulin resistance. Administration of insulin sensitizers has the potential to improve LVAD-mediated myocardial recovery in obese patients with HF.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1141-1164"},"PeriodicalIF":38.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124075","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":"Interventional MRI-Guided Ablation of Left Ventricular Tachycardia.","authors":"Luuk H G A Hopman,Marco J W Götte,Jules L Nelissen,Raschel D F van Luijk,Marjolein F Koster,Mika J Sybrandi,Katherine Lindborg,Pieter G Postema,Steven A J Chamuleau,Cornelis P Allaart,Michiel J B Kemme","doi":"10.1161/circulationaha.126.080380","DOIUrl":"https://doi.org/10.1161/circulationaha.126.080380","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"112 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147667020","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":"Risk of Heart Failure Hospitalization for GLP-1 Receptor Agonists Versus DPP-4 Inhibitors or SGLT-2 Inhibitors in Patients With Type 2 Diabetes: A Target Trial Emulation.","authors":"Yang Xu, Tao Huang, Yue Zhang, Dongze Ji, Katherine R Tuttle, Juan-Jesus Carrero, Edouard L Fu","doi":"10.1161/CIRCULATIONAHA.125.075157","DOIUrl":"10.1161/CIRCULATIONAHA.125.075157","url":null,"abstract":"<p><strong>Background: </strong>Novel treatments are needed for the primary and secondary prevention of heart failure in patients with type 2 diabetes, including individuals with and those without a history of heart failure. Conflicting trial evidence exists on whether glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of hospitalization for heart failure (HHF) in this broad population and whether this is a class effect or varies by specific agent. Furthermore, their comparative effectiveness against sodium-glucose cotransporter-2 inhibitors (SGLT-2is) is unknown.</p><p><strong>Methods: </strong>We emulated 2 target trials using population-based health care data from Stockholm, Sweden (2010-2021). Target trial 1 included adult patients with type 2 diabetes who newly initiated GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP-4is), and target trial 2 compared GLP-1RA with SGLT-2i. The primary outcome was HHF. Cox regression was used to estimate intention-to-treat hazard ratios, with inverse probability of treatment weighting used to balance 72 confounders. Major adverse cardiovascular events were used as the positive control outcome. Analyses were conducted for the GLP-1RA class overall and for individual agents, including liraglutide and semaglutide.</p><p><strong>Results: </strong>Target trial 1 included 32 979 patients (42% GLP-1RA and 58% DPP-4i) with a mean age of 64 years and 40% female; and target trial 2 included 30 104 patients (49% GLP-1RA and 51% SGLT-2i) with a mean age of 63 years and 38% female. Starting a GLP-1RA was associated with a lower 3-year absolute risk of HHF than starting a DPP-4i (3.4% versus 4.3%), corresponding to a weighted hazard ratio of 0.77 (95% CI, 0.66-0.91). Absolute 3-year risks for GLP-1RA compared with SGLT-2i on HHF were 3.6% and 3.3% with a weighted hazard ratio of 1.02 (95% CI, 0.85-1.18). The absolute risk difference was largest for patients with higher predicted risk of heart failure at baseline. Results were consistent for single agents, in per-protocol analyses, and in the majority of subgroups. In positive control outcome analyses, GLP-1RA use was associated with a lower rate of major adverse cardiovascular events than DPP-4i use (weighted hazard ratio, 0.85 [95% CI, 0.74-0.99]), consistent with trial findings.</p><p><strong>Conclusions: </strong>GLP-1RA use is associated with a lower risk of HHF compared with DPP-4i and similar risks compared with SGLT-2i in routine clinical care for patients with type 2 diabetes.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1086-1100"},"PeriodicalIF":38.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275909","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":"Correction to: 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.","authors":"Daniel W Jones, Keith C Ferdinand, Sandra J Taler, Heather M Johnson, Daichi Shimbo, Marwah Abdalla, M Martine Altieri, Nisha Bansal, Natalie A Bello, Adam P Bress, Jocelyn Carter, Jordana B Cohen, Karen J Collins, Yvonne Commodore-Mensah, Leslie L Davis, Brent Egan, Sadiya S Khan, Donald M Lloyd-Jones, Bernadette Mazurek Melnyk, Eva A Mistry, Modele O Ogunniyi, Stacey L Schott, Sidney C Smith, Amy W Talbot, Wanpen Vongpatanasin, Karol E Watson, Paul K Whelton, Jeff D Williamson","doi":"10.1161/CIR.0000000000001436","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001436","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"153 15","pages":"e1121"},"PeriodicalIF":38.6,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670933","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 Zhuang et al Regarding Article, \"Experiences of Stalking and Obtaining a Restraining Order Are Associated With Onset of Cardiovascular Events in Women: A Prospective Analysis in the Nurses' Health Study II\".","authors":"Ziye Zhuang,Jinbang Huang,Hao Chi","doi":"10.1161/circulationaha.125.077035","DOIUrl":"https://doi.org/10.1161/circulationaha.125.077035","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"21 1","pages":"e1117-e1118"},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666576","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":"Dysregulated Aldosterone Production in Obesity Is Associated With Adverse Cardiac Structure, Function, and Adiposity.","authors":"Cheng-Hsuan Tsai,Justin M Chan,Julia Milks,Arnaldo Ferrebus,Isabelle Hanna,Sanan Mahrokhian,Andrew J Newman,Stéfanie Parisien-La Salle,Isabela Reis Marques,Kristen Foote,Gail K Adler,Raymond Y Kwong,Michael Jerosch-Herold,Bertram Pitt,Anand Vaidya,Jenifer M Brown","doi":"10.1161/circulationaha.125.078143","DOIUrl":"https://doi.org/10.1161/circulationaha.125.078143","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"278 1","pages":"1174-1177"},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666575","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":"Culinary Medicine as a Key Lever in Hypertension Management.","authors":"Nicole Farmer,Yinying Wei,Jaclyn Lewis Albin","doi":"10.1161/circulationaha.125.078530","DOIUrl":"https://doi.org/10.1161/circulationaha.125.078530","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"134 1","pages":"1083-1085"},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666577","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":"GLP-1RA Use and the Risk of Heart Failure in Patients With Diabetes: Association or Causation?","authors":"Kosuke Inoue,Dhruv S Kazi","doi":"10.1161/circulationaha.126.078150","DOIUrl":"https://doi.org/10.1161/circulationaha.126.078150","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"193 1","pages":"1101-1103"},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666573","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 Murchland et al to Letter Regarding Article, \"Experiences of Stalking and Obtaining a Restraining Order Are Associated With Onset of Cardiovascular Events in Women: A Prospective Analysis in the Nurses' Health Study II\".","authors":"Audrey R Murchland,Karestan C Koenen,Rebecca B Lawn","doi":"10.1161/circulationaha.126.078389","DOIUrl":"https://doi.org/10.1161/circulationaha.126.078389","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"431 1","pages":"e1119-e1120"},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147666578","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-Specific Targeting of Different Smooth Muscle Cell Populations by Intersectional Genetics.","authors":"Lei Wang,Maximilian Staps,Stefan Günther,Elie El Agha,Saverio Bellusci,Carsten Kuenne,Junhua Du,Andre Schneider,Thomas Braun","doi":"10.1161/circulationaha.125.076318","DOIUrl":"https://doi.org/10.1161/circulationaha.125.076318","url":null,"abstract":"BACKGROUNDThe Cre/loxP recombination system is the main tool for cell type-specific lineage tracing and gene targeting. Currently available smooth muscle cell (SMC)-specific Cre mouse lines show off-target activity outside the SMC lineage and are unable to distinguish among arterial SMCs (ASMCs), venous SMCs, and nonvascular SMCs (NVSMCs). These limitations prevent ASMC- and NVSMC-specific gene targeting, which is required to characterize the role of SMCs in different organs and diseases.METHODSTo achieve precise manipulation of ASMCs in vivo, we combined alleles for Cspg4-Dre and rox-Stop-containing Acta2-CreER (Acta2-rox-CreER), generating a mouse line with Cre activity exclusively in ASMCs. RNA sequencing of fluorescence-activated cell sorting-isolated ASMCs was used to reveal differences in ASMCs among multiple organs. To specifically target and characterize NVSMCs in different organs, a combination of Chrm2-Dre and Acta2-rox-CreER was used. Disease-specific transcriptional changes of pulmonary ASMCs and NVSMCs were determined in the Sugen 5416/hypoxia model of pulmonary arterial hypertension. Usefulness for functional studies was assessed by inactivation of the genes for the splicing factors RBPMS (RNA-binding protein with multiple splicing) and RBPMS2 (RNA-binding protein with multiple splicing 2) in ASMCs.RESULTSIntersectional genetic approaches using Cspg4-Dre and Acta2-rox-CreER mouse lines specifically targeted ASMCs within various organs. A combination of Chrm2-Dre with Acta2-rox-CreER achieved specific targeting of NVSMCs. Transcriptomic profiling revealed distinct gene expression signatures in ASMCs of different organs, indicating organ-dependent transcriptional adaptation of ASMCs. Transcriptional differences among NVSMCs were found in the lung, intestine, and bladder. Activation of distinct pathways was uncovered in pulmonary ASMCs and bronchial SMCs after induction of pulmonary arterial hypertension. Inactivation of Rbpms and Rbpms2 in ASMCs increased thickness of the muscular layer in pulmonary arteries, whereas inactivation in all SMCs abolished the contractile phenotype of NVSMCs in the intestine.CONCLUSIONSThe successful generation of mouse lines specifically targeting different subtypes of SMCs enhances specificity, allowing distinction between vascular and nonvascular effects of diseased SMCs. The identification of vessel bed-specific gene signatures will pave the way for specific manipulation of SMCs in distinct diseased organs, such as the lung in pulmonary arterial hypertension.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"193 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663779","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}