JACC: Basic to Translational Science最新文献_第2页

Molecular Synergy and Inflammatory Activation in Pathogenesis and Therapy of Atrial Cardio-Metabolic Cardiomyopathy 心房心代谢性心肌病发病与治疗中的分子协同作用与炎症激活

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-09-01 Epub Date: 2026-08-24 DOI: 10.1016/j.jacbts.2026.101661

Jean-Baptiste Guichard MD, PhD, Stanley Nattel MD

引用次数: 0

Recognizing Early Career Translational Investigators 认识早期职业翻译研究者。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-09-01 Epub Date: 2026-09-28 DOI: 10.1016/j.jacbts.2026.101712

Matthias Nahrendorf MD (Editor-in-Chief,JACC: Basic to Translational Science)

引用次数: 0

SGLT2-Inhibitors and Molecular Signatures of Aortic Valve Remodeling in Severe Aortic Stenosis: The Valve-AS Study. sglt2抑制剂和严重主动脉瓣狭窄主动脉瓣重构的分子特征：瓣膜as研究。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-11 DOI: 10.1016/j.jacbts.2026.101658

Pasquale Paolisso, Lucia Scisciola, Manuela Giovanna Basilicata, Emanuela Salviati, Marta Belmonte, Leen Delrue, Giuseppe Comentale, Pasquale Policastro, Marco Redivo, Linda Piras, Francesco Zito, Marco Coli, Raffaella Mistrulli, Rashmi Joshi, Emanuele Gallinoro, Luca Bergamaschi, Carmine Pizzi, Filip Casselman, Bernard Stockman, Giovanna Aquino, Antonio Pio Montella, Michele Torella, Marisa De Feo, Emanuele Pilato, Jozef Bartunek, Eduardo Maria Somella, Pietro Campiglia, Raffaele Marfella, Marc Vanderheyden, Giuseppe Paolisso, Emanuele Barbato, Giovanni Melina, Michelangela Barbieri

{"title":"SGLT2-Inhibitors and Molecular Signatures of Aortic Valve Remodeling in Severe Aortic Stenosis: The Valve-AS Study.","authors":"Pasquale Paolisso, Lucia Scisciola, Manuela Giovanna Basilicata, Emanuela Salviati, Marta Belmonte, Leen Delrue, Giuseppe Comentale, Pasquale Policastro, Marco Redivo, Linda Piras, Francesco Zito, Marco Coli, Raffaella Mistrulli, Rashmi Joshi, Emanuele Gallinoro, Luca Bergamaschi, Carmine Pizzi, Filip Casselman, Bernard Stockman, Giovanna Aquino, Antonio Pio Montella, Michele Torella, Marisa De Feo, Emanuele Pilato, Jozef Bartunek, Eduardo Maria Somella, Pietro Campiglia, Raffaele Marfella, Marc Vanderheyden, Giuseppe Paolisso, Emanuele Barbato, Giovanni Melina, Michelangela Barbieri","doi":"10.1016/j.jacbts.2026.101658","DOIUrl":"https://doi.org/10.1016/j.jacbts.2026.101658","url":null,"abstract":"<p><p>Sodium-glucose cotransporter 2 inhibitor (SGLT2i) exerts pleiotropic metabolic and anti-inflammatory effects, but its role in calcific aortic valve stenosis (CAVS) is unclear. In this multicenter prospective study, 83 patients with severe CAVS undergoing surgical aortic valve replacement were stratified by SGLT2i use. Explanted valve tissue and plasma were analyzed using transcriptomics, circulating biomarkers, and metabolomics, including MALDI-MSI. SGLT2i therapy was associated with reduced valvular expression of SGLT1/2, GLUT4, and NHE, increased PPARα, decreased PPARγ, attenuation of inflammatory signaling (lower NF-κB and IL-6), and oxidative stress response (higher SOD2). Extracellular matrix turnover and fibrocalcific remodeling enzymes (MMP-9 and MMP-12) were also reduced. Metabolomic profiling demonstrated distinct clustering, with enrichment of amino acid and redox pathways in SGLT2i users. These findings suggest that SGLT2i therapy is associated with coordinated molecular and metabolic reprogramming of the valvular microenvironment, supporting a potential disease-modifying role in CAVS.</p>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":" ","pages":"101658"},"PeriodicalIF":8.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840116","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}

引用次数: 0

The Orally Available Ghrelin Receptor-Agonist AC01 Improves Systolic Function in HFrEF Mice and Nonhuman Primates 口服胃饥饿素受体激动剂AC01改善HFrEF小鼠和非人灵长类动物的收缩功能。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-07-22 DOI: 10.1016/j.jacbts.2026.101635

Lars H. Lund MD, PhD, Camilla Hage PhD, Mattias Carlström PhD, Pascal Champéroux PhD, Marcus Ståhlberg MD, PhD, Patrik Strömberg PhD, Göran Westerberg PhD, Emanuela Lovati PhD, Allan Gordon MD, PhD, Johan Sjödahl PhD, Daniel C. Andersson MD, PhD, Gianluigi Pironti PhD

{"title":"The Orally Available Ghrelin Receptor-Agonist AC01 Improves Systolic Function in HFrEF Mice and Nonhuman Primates","authors":"Lars H. Lund MD, PhD, Camilla Hage PhD, Mattias Carlström PhD, Pascal Champéroux PhD, Marcus Ståhlberg MD, PhD, Patrik Strömberg PhD, Göran Westerberg PhD, Emanuela Lovati PhD, Allan Gordon MD, PhD, Johan Sjödahl PhD, Daniel C. Andersson MD, PhD, Gianluigi Pironti PhD","doi":"10.1016/j.jacbts.2026.101635","DOIUrl":"10.1016/j.jacbts.2026.101635","url":null,"abstract":"<div><div>Heart failure with reduced ejection fraction (HFrEF) is characterized by impaired cardiac contractility. AC01, a small-molecule ghrelin receptor agonist, enhances contractility in cardiomyocytes. This study evaluated the in vivo hemodynamic effects of AC01 in a mouse HFrEF model and in cynomolgus monkeys. In HFrEF mice, intravenous AC01 significantly increased cardiac output, stroke volume, and ejection fraction versus vehicle, without any apparent detriment to diastolic function. Pressure-volume loop analysis demonstrated load-independent inotropic effects. In monkeys, oral AC01 increased cardiac output and stroke volume while reducing heart rate, without lowering central aortic pressure. These effects were sustained over 14 days of oral dosing. Additionally, AC01 improved autonomic balance by increasing parasympathetic and decreasing sympathetic activity. Overall, AC01 produced rapid, consistent, and sustained improvements in systolic function across species, supporting its potential as a novel, load-independent inotropic therapy for heart failure.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 8","pages":"Article 101635"},"PeriodicalIF":8.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148561968","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}

引用次数: 0

Disrupted Mitochondrial Quality Control in Atherosclerotic Disease 动脉粥样硬化疾病中线粒体质量控制中断：线粒体自噬和动力学焦点。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-07-23 DOI: 10.1016/j.jacbts.2026.101625

Taylor Wilcox BS, Julie Hansen MD, Andrew Blanker BS, Michael E. Widlansky MD, MPH

引用次数: 0

PD-1/PD-L1 Signaling in Non-ICI Myocarditis PD-1/PD-L1信号在非ici心肌炎中的作用。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-04-19 DOI: 10.1016/j.jacbts.2026.101539

Laura I. Yousif MSc, Aukje G. Sijtema MSc, Ymke Appels MSc, Pieter F. van den Berg MD, Joseph Pierre Aboumsallem PhD, Olivier C. Manintveld MD, PhD, Dirk J. Duncker MD, PhD, Rudolf A. de Boer MD, PhD, Wouter C. Meijers MD, PhD

{"title":"PD-1/PD-L1 Signaling in Non-ICI Myocarditis","authors":"Laura I. Yousif MSc, Aukje G. Sijtema MSc, Ymke Appels MSc, Pieter F. van den Berg MD, Joseph Pierre Aboumsallem PhD, Olivier C. Manintveld MD, PhD, Dirk J. Duncker MD, PhD, Rudolf A. de Boer MD, PhD, Wouter C. Meijers MD, PhD","doi":"10.1016/j.jacbts.2026.101539","DOIUrl":"10.1016/j.jacbts.2026.101539","url":null,"abstract":"<div><div>Immune checkpoint inhibitor (ICI)-mediated myocarditis is a notorious complication of cancer treatment; however, the role of immune checkpoints in the heart during inflammation remains unknown. We investigated myocardial expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in non-ICI myocarditis. We performed a cross-species single-cell/-nucleus RNA sequencing comparative analysis, including 3 different models of myocarditis in mice and human hearts, with in vitro validation in human cells. This provided compelling evidence that PD-1/PD-L1 signaling in both murine and human non-ICI myocarditis is inherent to the myocardial inflammatory response. Specifically, cardiac endothelial cells and fibroblasts exhibited robust and sustained PD-L1 up-regulation in myocarditis, while also coinciding temporally with peak PD-1 expression on T cells, which presents an important defense mechanism. Therefore, immune checkpoints have global importance in myocarditis and may serve as a therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 8","pages":"Article 101539"},"PeriodicalIF":8.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723050","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}

引用次数: 0

Interplay Between Interleukin-6 Receptor and Lipoprotein(a) in the Causal Association With Cardiovascular Disease 白细胞介素-6受体与脂蛋白(a)在心血管疾病中的相互作用

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-08-24 DOI: 10.1016/j.jacbts.2026.101630

Ruth Frikke-Schmidt MD, PhD, DMSci

引用次数: 0

Proteomic Signatures of High-Risk Coronary Plaque Features and Incident Events 高危冠状动脉斑块特征和事件的蛋白质组学特征。

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-07-22 DOI: 10.1016/j.jacbts.2026.101640

Anish Karpurapu BSE, Lydia Coulter Kwee PhD, Caroline de Calvacamp MS, Elizabeth Zhao MD, Kristin Corey MD, Khurram Nasir MD, Maros Ferencik MD, PhD, MCR, Mette Nyegaard PhD, Peter Loof Møller PhD, Palle Duun Rohde PhD, Hannes Helgason PhD, Morten Bøttcher MD, PhD, Simon Winther MD, PhD, DmSci, Borek Foldyna MD, Pamela S. Douglas MD, Svati H. Shah MD, MHSc

{"title":"Proteomic Signatures of High-Risk Coronary Plaque Features and Incident Events","authors":"Anish Karpurapu BSE, Lydia Coulter Kwee PhD, Caroline de Calvacamp MS, Elizabeth Zhao MD, Kristin Corey MD, Khurram Nasir MD, Maros Ferencik MD, PhD, MCR, Mette Nyegaard PhD, Peter Loof Møller PhD, Palle Duun Rohde PhD, Hannes Helgason PhD, Morten Bøttcher MD, PhD, Simon Winther MD, PhD, DmSci, Borek Foldyna MD, Pamela S. Douglas MD, Svati H. Shah MD, MHSc","doi":"10.1016/j.jacbts.2026.101640","DOIUrl":"10.1016/j.jacbts.2026.101640","url":null,"abstract":"<div><div>Patients with and without obstructive coronary artery disease (oCAD) experience heterogeneous cardiovascular risk, and coronary computed tomography angiography (CCTA) high-risk plaque features are not universally available. This study evaluated whether circulating proteomic profiles clarify plaque biology and improve risk assessment. Proteomic profiling of 572 proteins was performed in PROMISE (N = 1,724), with validation in Dan-NICAD (N = 2,743) and UK Biobank (N = 53,018). A high-risk composite phenotype (HRCP) combined oCAD, high stenosis or plaque burden, high coronary calcium, and high-risk plaque features. Thirty-seven proteins were independently associated with HRCP and were mapped to inflammatory, metabolic, and proteolytic pathways; 7 were also associated with major adverse cardiovascular events, including lipoprotein lipase and cathepsin D. While the 37-protein score added little discrimination beyond clinical factors, it improved reclassification (net reclassification index = 0.13, <em>P</em> < 0.001), suggesting proteomic profiles may complement clinical models while elucidating disease biology and highlighting cathepsin D as a potential therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 8","pages":"Article 101640"},"PeriodicalIF":8.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562188","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}

引用次数: 0

IL-1–Activated Inflammatory Cardiac Fibroblasts Exacerbate Acute Coxsackievirus B3 Myocarditis il -1激活的炎性心脏成纤维细胞加重急性柯萨奇病毒B3心肌炎

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-07-23 DOI: 10.1016/j.jacbts.2026.101637

David S. Elias MD, PhD, Wonyoung Jo MS, Monica V. Talor MS, Camille Jaime BS, Abdel Daoud MS, Ina Sulkaj PhD, Martin Květoň RNDr., Nadan Wang MS, Ondřej Fabián MD, PhD, Vojtěch Melenovský MD, PhD, Daniela Čiháková MD, PhD

{"title":"IL-1–Activated Inflammatory Cardiac Fibroblasts Exacerbate Acute Coxsackievirus B3 Myocarditis","authors":"David S. Elias MD, PhD, Wonyoung Jo MS, Monica V. Talor MS, Camille Jaime BS, Abdel Daoud MS, Ina Sulkaj PhD, Martin Květoň RNDr., Nadan Wang MS, Ondřej Fabián MD, PhD, Vojtěch Melenovský MD, PhD, Daniela Čiháková MD, PhD","doi":"10.1016/j.jacbts.2026.101637","DOIUrl":"10.1016/j.jacbts.2026.101637","url":null,"abstract":"<div><div>We investigated how inflammatory fibroblasts (IFs) contribute to acute viral myocarditis, a dangerous inflammatory heart disease often caused by infections like coxsackievirus B3 (CVB3). Using CCL2-mCherry reporter mice, we tracked IF kinetics during CVB3 infection and discovered that their activity peaks on day 3 of myocarditis and is characterized by the production of Th1, Th2, and Th17 chemokines rather than typical profibrotic genes. We identified IL-1β as the most potent activator of this inflammatory state. We generated PDGFRα<sup>cre</sup>IL1r1<sup>fl/fl</sup> mice to specifically delete IL-1 signaling in fibroblasts. This targeted deletion reduced total cardiac inflammation by 45%—specifically lowering monocytes, T cells, and NK cells—without affecting viral clearance. By confirming the presence of IFs in endomyocardial biopsies from human patients, we have shown that fibroblast-specific IL-1 signaling is a critical driver of disease and a potential therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 8","pages":"Article 101637"},"PeriodicalIF":8.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148578810","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}

引用次数: 0

Functional Autoantibodies in Myocardial Diseases 心肌疾病中的功能性自身抗体

IF 8.4 1区医学

JACC: Basic to Translational Science Pub Date : 2026-08-01 Epub Date: 2026-07-24 DOI: 10.1016/j.jacbts.2026.101636

Simon Vanhentenrijk MD PharmD, Silvio Nunes Augusto Jr. MA, Jennifer Wilcox BS, Chia-Feng Liu PhD, W.H. Wilson Tang MD

{"title":"Functional Autoantibodies in Myocardial Diseases","authors":"Simon Vanhentenrijk MD PharmD, Silvio Nunes Augusto Jr. MA, Jennifer Wilcox BS, Chia-Feng Liu PhD, W.H. Wilson Tang MD","doi":"10.1016/j.jacbts.2026.101636","DOIUrl":"10.1016/j.jacbts.2026.101636","url":null,"abstract":"<div><div>Myocardial autoimmune responses result in distinctive cardiac diseases and are associated with poor clinical outcomes. Autoantibodies (AAbs) play a crucial role in myocardial humoral autoimmunity by targeting endogenous tissue, or “self-antigens.” Myocardial tissue injury or myocyte disarray caused by AAbs triggers a cascade of defensive immunological responses that may lead to worsening biventricular remodeling. However, over the past decade, the concept of AAbs in myocardial diseases has shifted from viewing AAbs as uniformly deleterious to a more nuanced explanation of AAbs influencing downstream intracellular pathways with multiple possible outcomes. This paradigm shift arose from technological advances such as large language models for accelerated epitope screening and high-throughput protein assays that uncover complex autoimmune cross-reactivity and downstream intracellular signaling pathways. In this contemporary review article, we critically appraise the latest translational data on the role of AAbs in myocardial disease and provide a framework to encourage scientific endeavors in the development of new therapeutics for cardiomyopathies.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 8","pages":"Article 101636"},"PeriodicalIF":8.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148584439","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}

引用次数: 0