Circulation最新文献

{"title":"Exploring Origin-Dependent Susceptibility of Smooth Muscle Cells to Aortic Diseases Through Intersectional Genetics.","authors":"Ximeng Han, Yi Li, Enci Wang, Huan Zhu, Xiuzhen Huang, Wenjuan Pu, Mingjun Zhang, Kuo Liu, Huan Zhao, Zixin Liu, Yufei Zhao, Linghong Shen, Yan Li, Xiao Yang, Qing-Dong Wang, Xin Ma, Ruling Shen, Kathy O Lui, Lixin Wang, Ben He, Bin Zhou","doi":"10.1161/CIRCULATIONAHA.124.070782","DOIUrl":"10.1161/CIRCULATIONAHA.124.070782","url":null,"abstract":"<p><strong>Background: </strong>The developmental diversity among smooth muscle cells (SMCs) plays a crucial role in segment-specific aortic diseases. However, traditional genetic approaches are inadequate for enabling in vivo analysis of disease susceptibility associated with cellular origin. There is an urgent need to build genetic technologies that target different developmental origins to investigate the mechanisms of aortopathies, thereby facilitating the development of effective therapeutics.</p><p><strong>Methods: </strong>To address this challenge, we developed an advanced dual recombinase-mediated intersectional genetic system, specifically designed to precisely target SMCs from various developmental origins in mice. Specifically, we used <i>Isl1-Dre</i>, <i>Wnt1-Dre</i>, <i>Meox1-DreER</i>, and <i>Upk3b-Dre</i> to target SMC progenitors from the second heart field, cardiac neural crest, somites, and mesothelium, respectively. This system was combined with single-cell RNA sequencing to investigate the impact of TGF-β (transforming growth factor-β) signaling in different segments of the aorta by selectively knocking out Tgfbr2 in the ascending aorta and Smad4 in the aortic arch, respectively.</p><p><strong>Results: </strong>Through intersectional genetic approaches, we use the <i>Myh11-Cre(ER</i>) driver along with origin-specific Dre drivers to trace cells of diverse developmental origins within the SMC population. We found that a deficiency of Tgfbr2 in SMCs of the ascending aorta leads to aneurysm formation in this specific region. We also demonstrate the critical role of Smad4 in preserving aortic wall integrity and homeostasis in SMCs of the aortic arch.</p><p><strong>Conclusions: </strong>Our approach to genetically targeting SMC subtypes provides a novel platform for exploring origin-dependent or location-specific aortic vascular diseases. This genetic system enables comprehensive analysis of contributions from different cell lineages to SMC behavior and pathology, thereby paving the way for targeted research and therapeutic interventions in the future.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1248-1267"},"PeriodicalIF":35.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381739","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 Bonnesen et al to Letter Regarding Article, \"Comparative Cardiovascular Effectiveness of Empagliflozin Versus Dapagliflozin in Adults With Treated Type 2 Diabetes: A Target Trial Emulation\".","authors":"Kasper Bonnesen,Uffe Heide-Jørgensen,Morten Schmidt","doi":"10.1161/circulationaha.125.073970","DOIUrl":"https://doi.org/10.1161/circulationaha.125.073970","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"17 1","pages":"e964"},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889257","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 Dong et al Regarding Article, \"Comparative Cardiovascular Effectiveness of Empagliflozin Versus Dapagliflozin in Adults With Treated Type 2 Diabetes: A Target Trial Emulation\".","authors":"Jiayang Dong,Xinyue Yang,Wenjuan Zhang","doi":"10.1161/circulationaha.124.072362","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072362","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"69 1","pages":"e962-e963"},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889258","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":"Interplay Between Epicardial Adipose Tissue and Left Ventricular Stiffness in Heart Failure With Preserved Ejection Fraction.","authors":"Shiro Nakamori,Taku Omori,Naoki Fujimoto,Masaki Ishida,Yasutaka Ichikawa,Kakuya Kitagawa,Hajime Sakuma,Kaoru Dohi","doi":"10.1161/circulationaha.124.072866","DOIUrl":"https://doi.org/10.1161/circulationaha.124.072866","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"24 1","pages":"1294-1296"},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889209","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":"Splenic CD169⁺Tim4⁺ Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction.","authors":"Mohamed Ameen Ismahil, Guihua Zhou, Shreya Rajasekar, Min Gao, Shyam S Bansal, Bindiya Patel, Nita Limdi, Min Xie, Sergey Antipenko, Gregg Rokosh, Tariq Hamid, Sumanth D Prabhu","doi":"10.1161/CIRCULATIONAHA.124.071772","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071772","url":null,"abstract":"<p><strong>Background: </strong>Fidelity of wound healing after myocardial infarction (MI) is an important determinant of subsequent adverse cardiac remodeling and failure. Macrophages derived from infiltrating Ly6C^hi (lymphocyte antigen 6 complex, locus C) blood monocytes are a key component of this healing response; however, the importance of other macrophage populations is unclear.</p><p><strong>Methods: </strong>We used a variety of in vivo murine models and orthogonal approaches, including surgical MI, flow cytometry and single-cell RNA sequencing, lineage tracing and cell tracking, splenectomy, parabiosis, cell adoptive transfer, and functional characterization, to establish an essential role for splenic CD169⁺Tim4⁺ (cluster of differentiation 169⁺; T cell immunoglobulin- and mucin-domain-containing molecule 4) marginal metallophilic macrophages (MMMs) in post-MI wound healing in mice. Flow cytometry was used to measure circulating CD169⁺Tim4⁺ monocytes in humans with ST-segment-elevation MI and control participants with stable coronary artery disease undergoing elective percutaneous coronary intervention.</p><p><strong>Results: </strong>Splenic CD169⁺Tim4⁺ MMMs circulate in blood as Ly6C^low monocytes expressing macrophage markers and help populate CD169⁺Tim4⁺CCR2^-LYVE1^low macrophages in the naive heart. After acute MI, splenic MMMs augment phagocytosis and CCR (C-C motif chemokine receptor) 3 and CCR4 expression, and robustly mobilize to the heart, resulting in marked expansion of cardiac CD169⁺Tim4⁺LYVE1^low macrophages with an immunomodulatory and proresolving gene signature. These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation, and induction of a reparative macrophage phenotype in the infarcted heart. Splenic MMMs are both necessary and sufficient for post-MI wound healing, and limit late pathological remodeling. Liver X receptor-α agonist-induced expansion of the splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling. Humans with acute ST-segment-elevation MI also exhibit expansion of circulating CD169⁺Tim4⁺ cells, primarily within the intermediate (CD14⁺CD16⁺) monocyte population.</p><p><strong>Conclusions: </strong>Splenic CD169⁺Tim4⁺ MMMs are required for proresolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":""},"PeriodicalIF":35.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984044","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":"Suppression of the Prostaglandin I2-Type 1 Interferon Axis Induces Extramedullary Hematopoiesis to Promote Cardiac Repair After Myocardial Infarction.","authors":"Huizhen Lv,Chenchen Wang,Zening Liu,Meixi Quan,Kan Li,Fanglin Gou,Xuelian Shi,Qian Liu,Ying Yu,Ping Zhu,Hui Cheng,Tao Cheng,Ding Ai","doi":"10.1161/circulationaha.124.069420","DOIUrl":"https://doi.org/10.1161/circulationaha.124.069420","url":null,"abstract":"BACKGROUNDImmune cells are closely associated with all processes of cardiac repair after myocardial infarction (MI), including the initiation, development, and resolution of inflammation. Spleen extramedullary hematopoiesis (EMH) serves as a crucial source of emergency mature blood cells that are generated through the self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs). However, how EMH responds to MI and the role of EMH in cardiac repair after MI remains unclear.METHODSTo assess the role of spleen EMH in MI, a Tcf21CreER Scfflox/flox MI mouse model with inhibited EMH was constructed. GFP+ (green fluorescent protein) hematopoietic stem cells were sorted from eGFP (enhanced green fluorescent protein) mouse spleen by flow cytometry and injected into Tcf21CreER Scfflox/flox mice to test the sources of local inflammatory cells during MI. Using highly specific liquid chromatography-tandem mass spectrometry and single-cell RNA sequencing, we analyzed the lipidomic profile of arachidonic acid metabolites and the transcriptomes of HSPCs in the spleen after MI.RESULTSWe found that MI enhanced EMH, as reflected by the increase in spleen weight and volume and the number of HSPCs in the spleen. The lack of EMH in Scf-deficient mice exacerbated tissue injury after MI. Analysis of the transcriptome of spleen HSPCs after MI revealed that the type 1 interferon pathway was substantially inhibited in hematopoietic stem cell/multipotent progenitor subclusters, and the absence of type 1 interferon signaling enhanced the MI-induced spleen EMH. Lipidomics analysis revealed that prostaglandin I2 (PGI2) was markedly reduced in the spleen. PGI2 suppressed MI-induced EMH through a PGI2 receptor (IP)-cyclic adenosine monophosphate-453p-SP1 cascade in spleen HSPCs. Hematopoietic cell-specific IP-deficient mice exhibited enhanced EMH and improved cardiac recovery after MI.CONCLUSIONSTogether, our findings revealed that a PGI2-IFN axis was involved in spleen EMH after MI, providing new mechanistic insights into spleen EMH after MI and offering a new therapeutic target for treating ischemic cardiac injury.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"36 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885488","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":"A Plea for a Genetics-First Approach in Arrhythmogenic Cardiomyopathies.","authors":"Anneline S J M Te Riele,J Peter van Tintelen,Richard N W Hauer","doi":"10.1161/circulationaha.125.074022","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074022","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"36 1","pages":"1231-1234"},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889255","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":"New Tools for Precision Targeting of Origin-Specific Vascular Smooth Muscle Cells Using Intersectional Genetics.","authors":"Mark W Majesky","doi":"10.1161/circulationaha.125.073364","DOIUrl":"https://doi.org/10.1161/circulationaha.125.073364","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"140 1","pages":"1268-1271"},"PeriodicalIF":37.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889256","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":"COnventional vs. Optimized PERiprocedural Analgosedation vs. Total IntraVEnous Anesthesia for Pulsed-Field Ablation: a Three-Arm Randomized Controlled Trial (COOPERATIVE-PFA).","authors":"Veronika Sochorová,Veronika Kunštátová,Pavel OsmanČík,František Duška,Dalibor Heřman,Petr Waldauf,Lukáš Povišer,Jakub Karch,Lucie Znojilová,Věra Filipcová,Jana Hozmanová,Jana Veselá,Marek Hozman","doi":"10.1161/circulationaha.125.074427","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074427","url":null,"abstract":"BACKGROUNDDeep analgosedation (DAS) or general anesthesia (GA) is mandatory for pulsed-field ablation (PFA) of atrial fibrillation (AF). In contrast to DAS, GA (conventional or total intravenous anesthesia [TIVA]) requires airway management. To find the optimal sedation regimen, this study compared ketamine-remimazolam DAS and propofol-opioid TIVA to propofol-opioid DAS, focusing on sedation-related adverse events.METHODSPatients indicated for AF catheter ablation were randomly assigned in a 1:1:1 ratio to (1) DAS using intermittent propofol-opioid boluses (arm P), (2) continuous remimazolam-ketamine DAS (arm R), or (3) continuous propofol-opioid TIVA with secured airways (arm TIVA). Catheter ablation was performed using the FARAPULSE system (Boston Scientific, MA, USA). The major exclusion criterion was obstructive sleep apnea syndrome. The primary endpoint was defined as a composite of hypoxemia, hypotensive, or hypertensive events requiring intervention or leading to procedure discontinuation. Secondary endpoints included hemodynamic instability events, procedure time, serious adverse events, and patient satisfaction.RESULTSOne-hundred and twenty-seven patients (mean age 62.9 ± 10.3 years, 35.1% female, 47.2% with paroxysmal AF) were enrolled and randomized to the P (N = 42), R (N = 43) or TIVA (N = 42) arms. The primary endpoint occurred in 85.7% of P pts., 27.9% of R pts., and 66.7% of TIVA pts. (P < 0.001), driven by hypoxemia in the P arm (100% of pts. with the primary endpoint) and by hypotension in the TIVA arm (100%). The R arm showed a similar distribution of hypoxemia (50%) and hypotensive (66.7%) events. No differences were observed in mean procedural times, rates of serious adverse events, and assessment of patient satisfaction.CONCLUSIONSIn PFA procedures for AF, remimazolam-ketamine DAS was superior to propofol-opioid regimens (either boluses or continuous) and had the lowest risk of hypoxemia and hypotensive events. More than 80% of patients undergoing conventional propofol-opioid analgosedation experienced hypoxemia.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"24 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885490","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":"Stepwise Anatomical Approach to Ablation of Intramural Outflow Tract Ventricular Arrhythmias Guided by Septal Coronary Venous Mapping.","authors":"Andres Enriquez,Haran Yogasundaram,Victor Neira,Gustavo Guandalini,Timothy Markman,Poojita Shivamurthy,Matthew Hyman,Balaram Hanumanthu,David Lin,Robert Schaller,Gregory Supple,Sanjay Dixit,Rajat Deo,Saman Nazarian,Ramanan Kumareswaran,Michael Riley,Andrew E Epstein,Vincent See,Erica Zado,David Callans,David Frankel,Francis Marchlinski,Fermin Garcia","doi":"10.1161/circulationaha.125.074175","DOIUrl":"https://doi.org/10.1161/circulationaha.125.074175","url":null,"abstract":"BACKGROUNDIntramural site of origin is a major cause of ablation failure of ventricular arrhythmias and the optimal strategy is unclear. This study investigated the efficacy of a stepwise ablation approach for intramural outflow tract (OT) premature ventricular complexes (PVCs) guided by mapping of the septal coronary venous system.METHODSConsecutive patients with OT PVCs were included in which an intramural origin was confirmed by demonstration of earliest activation in a septal coronary vein. Radiofrequency ablation was performed from the closest endocardial site in the left (LVOT) and/or right ventricular OT (RVOT) independent of the local activation time. If there was no suppression by endocardial ablation, retrograde transvenous ethanol infusion with a single or double balloon technique was performed, targeting the earliest septal coronary vein. If venous anatomy was not suitable for ethanol ablation or if this failed, bipolar ablation was performed.RESULTSSixty patients (age 61±12 years, 78% male) were included. The mean QRS duration of the PVC was 150.8±17.6 ms with a maximum deflection index of 0.51±0.11, and the most common ECG pattern was a left bundle branch block with inferior axis and V3 transition (63%) followed by a right bundle branch block with inferior axis and no transition (27%). Earliest ventricular activation (28.6±11.2 ms pre-QRS) was recorded in the left ventricular annular vein in 15 cases and a septal perforator vein in 45 cases. Acute PVC suppression at the end of the procedure was achieved in all cases. In 87% of cases (n=52), endocardial ablation from the endocardial LVOT, RVOT or both was successful in eliminating the PVC. In the remaining 8 patients, the PVC was eliminated with ethanol infusion (n=7) and bipolar ablation (n=1). Complications included one case of pericardial effusion related to venous mapping. During follow-up (17±24 months), the PVC burden was reduced from 28±12% to 2.3±4.7% and long-term success (≥80% burden reduction) was 88%.CONCLUSIONSMost intramural OT PVCs can be successfully eliminated with endocardial ablation adjacent to the earliest intramural activation site. A high success rate is achieved when following a stepwise approach, with bailout ablation strategies required in a minority of cases.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"43 1","pages":""},"PeriodicalIF":37.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885491","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}