Circulation最新文献

{"title":"S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.","authors":"Dorothea Kehr, Julia Ritterhoff, Manuel Glaser, Lukas Jarosch, Rafael E Salazar, Kristin Spaich, Karl Varadi, Jennifer Birkenstock, Michael Egger, Erhe Gao, Walter J Koch, Max Sauter, Marc Freichel, Hugo A Katus, Norbert Frey, Andreas Jungmann, Cornelius Busch, Paul J Mather, Arjang Ruhparwar, Martin Busch, Mirko Völkers, Rebecca C Wade, Patrick Most","doi":"10.1161/CIRCULATIONAHA.123.066961","DOIUrl":"10.1161/CIRCULATIONAHA.123.066961","url":null,"abstract":"<p><strong>Background: </strong>The EF-hand Ca²⁺ sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca²⁺ ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.</p><p><strong>Methods: </strong>We applied an integrative translational research pipeline ranging from in silico computational molecular modeling and in vitro biochemical molecular assays as well as isolated rodent and human cardiomyocyte performance assessments to in vivo safety and efficacy studies in small and large animal cardiac disease models.</p><p><strong>Results: </strong>We characterize S100A1ct as a cell-penetrating peptide with positive inotropic and antiarrhythmic properties in normal and failing myocardium in vitro and in vivo. This activity translates into improved contractile performance and survival in preclinical heart failure models with reduced ejection fraction after S100A1ct systemic administration. S100A1ct exerts a fast and sustained dose-dependent enhancement of cardiomyocyte Ca²⁺ cycling and prevents β-adrenergic receptor-triggered Ca²⁺ imbalances by targeting SERCA2a and RyR2 activity. In line with the S100A1ct-mediated enhancement of SERCA2a activity, modeling suggests an interaction of the peptide with the transmembrane segments of the sarcoplasmic Ca²⁺ pump. Incorporation of a cardiomyocyte-targeting peptide tag into S100A1ct (cor-S100A1ct) further enhanced its biological and therapeutic potency in vitro and in vivo.</p><p><strong>Conclusions: </strong>S100A1ct is a promising lead for the development of novel peptide-based therapeutics against heart failure with reduced ejection fraction.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"548-565"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680976","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":"Coronary CT Anatomy-Based Prediction of Invasively Assessed Hemodynamic Significance in Middle-Aged Patients With Right Coronary Artery Anomaly: The NARCO Study.","authors":"Anselm W Stark, René L Matthey-de-l'Endroit, Adriana Ferroni, Ryota Kakizaki, Marius R Bigler, Flavio G Biccirè, Yasushi Ueki, Andreas Haeberlin, Matthias Siepe, Isaac Shiri, Stephan Windecker, Lorenz Räber, Christoph Gräni","doi":"10.1161/CIRCULATIONAHA.124.071637","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.071637","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"578-580"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491027","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":"CXCL12 Derived From ACKR1⁺ Intraplaque Neovessels Mediates CD8⁺ T Cell Recruitment in Human Atherosclerosis.","authors":"Laura Parma, Nadja Sachs, Nikola Sobczak, Zhaolong Li, Kevin Merchant, Jessica Pauli, Marie A C Depuydt, Anouk Wezel, Harm J Smeets, Ilze Bot, Bram Slütter, Lars Maegdefessel, Christian Weber, Johan Duchêne, Remco T A Megens","doi":"10.1161/CIRCULATIONAHA.124.072560","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072560","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"581-584"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491062","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":"Digital Twins: The Future for Ventricular Tachycardia Ablation?","authors":"Dingxin Qin, Jagmeet P Singh","doi":"10.1161/CIRCULATIONAHA.124.072299","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.124.072299","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"534-536"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491065","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":"Highlights From the <i>Circulation</i> Family of Journals.","authors":"","doi":"10.1161/CIRCULATIONAHA.125.073856","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.073856","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"568-573"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673506","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: Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association.","authors":"","doi":"10.1161/CIR.0000000000001313","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001313","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"e677-e679"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491032","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":"State of the Heart (and Brain) in 2025.","authors":"Dhruv S Kazi","doi":"10.1161/CIRCULATIONAHA.125.073826","DOIUrl":"10.1161/CIRCULATIONAHA.125.073826","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"515-517"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045697","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":"Highlights From the <i>Circulation</i> Family of Journals.","authors":"","doi":"10.1161/CIRCULATIONAHA.125.073856","DOIUrl":"https://doi.org/10.1161/CIRCULATIONAHA.125.073856","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"568-573"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491091","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: Abstract 4139303: Temporal Trends in Cardiovascular Risk Factors and Cardiovascular Disease among Middle Eastern Immigrants in the National Health Interview Survey 2004-2018.","authors":"","doi":"10.1161/CIR.0000000000001311","DOIUrl":"https://doi.org/10.1161/CIR.0000000000001311","url":null,"abstract":"","PeriodicalId":10331,"journal":{"name":"Circulation","volume":"151 8","pages":"e680"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491029","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":"Personalized Heart Digital Twins Detect Substrate Abnormalities in Scar-Dependent Ventricular Tachycardia.","authors":"Michael C Waight, Adityo Prakosa, Anthony C Li, Nick Bunce, Anna Marciniak, Natalia A Trayanova, Magdi M Saba","doi":"10.1161/CIRCULATIONAHA.124.070526","DOIUrl":"10.1161/CIRCULATIONAHA.124.070526","url":null,"abstract":"<p><strong>Background: </strong>Current outcomes from catheter ablation for scar-dependent ventricular tachycardia (VT) are limited by high recurrence rates and long procedure durations. Personalized heart digital twin technology presents a noninvasive method of predicting critical substrate in VT, and its integration into clinical VT ablation offers a promising solution. The accuracy of the predictions of digital twins to detect invasive substrate abnormalities is unknown. We present the first prospective analysis of digital twin technology in predicting critical substrate abnormalities in VT.</p><p><strong>Methods: </strong>Heart digital twin models were created from 18 patients with scar-dependent VT undergoing catheter ablation. Contrast-enhanced cardiac magnetic resonance images were used to reconstruct finite-element meshes, onto which regional electrophysiological properties were applied. Rapid-pacing protocols were used to induce VTs and to define the VT circuits. Predicted optimum ablation sites to terminate all VTs in the models were identified. Invasive substrate mapping was performed, and the digital twins were merged with the electroanatomical map. Electrogram abnormalities and regions of conduction slowing were compared between digital twin-predicted sites and nonpredicted areas.</p><p><strong>Results: </strong>Electrogram abnormalities were significantly more frequent in digital twin-predicted sites compared with nonpredicted sites (468/1029 [45.5%] versus 519/1611 [32.2%]; <i>P</i><0.001). Electrogram duration was longer at predicted sites compared with nonpredicted sites (82.0±25.9 milliseconds versus 69.7±22.3 milliseconds; <i>P</i><0.001). Digital twins correctly identified 21 of 26 (80.8%) deceleration zones seen on isochronal late activation mapping.</p><p><strong>Conclusions: </strong>Digital twin-predicted sites display a higher prevalence of abnormal and prolonged electrograms compared with nonpredicted sites and accurately identify regions of conduction slowing. Digital twin technology may help improve substrate-based VT ablation.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT04632394.</p>","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"521-533"},"PeriodicalIF":35.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930736","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}