Cardiovascular Research最新文献

{"title":"Atrial remodelling and atrial fibrillation self-sustaining: the role of circulating circDGCR8","authors":"Yuanfeng Gao, Ying Dong, Nan Jiang, Hanrui Zhang, Zheng Liu, Qianhui Wang, Yuan Fu, Jing Li, Zhiqing Li, Huize Pan, Xianing Zheng, Lingyu Zhan, Xinchun Yang, Li Xu, Mulei Chen","doi":"10.1093/cvr/cvaf060","DOIUrl":"https://doi.org/10.1093/cvr/cvaf060","url":null,"abstract":"Aims The prediction of atrial fibrillation (AF) progression and post-ablation recurrence is currently based on empirical estimates, leading to suboptimal predictive accuracy. This study investigates whether atrial remodelling, a key factor in the severity of atrial cardiomyopathy, could serve as a shared substrate influencing both AF progression and recurrence. We aimed to identify circular RNAs (circRNAs) associated with atrial remodelling and to evaluate their ability to predict AF progression and recurrence. Methods and results We assessed the differential expression of plasma circRNAs between paroxysmal (PAF) and persistent AF (PsAF) patients using microarray analysis. Selected candidate circRNAs were validated through qPCR following rigorous statistical and bioinformatics analysis. circDGCR8 was consistently found to be up-regulated in PsAF compared with PAF patients. Additionally, circDGCR8 was significantly up-regulated in human atrial fibroblasts treated with angiotensin II (AngII). Gain- and loss-of-function studies suggested that circDGCR8 could promote atrial remodelling at cellular level by enhancing collagen production and fibroblast proliferation. Overexpression of circDGCR8 in human cardiac fibroblasts significantly altered the gene expression spectrum, impacting pathways including IL-17 signalling and TNF signalling. Moreover, circDGCR8 levels were positively correlated with atrial fibrosis, as indicated by increased percentages of low voltage zones. The predictive value of circDGCR8 was evaluated in two cohorts: (i) PAF patients monitored for 36 months with progression to PsAF as the endpoint, and (ii) AF patients who underwent radiofrequency ablation followed for 12 months to assess recurrence. In both cohorts, higher level of circDGCR8 was associated with increased risks of AF progression and post-ablation recurrence. Conclusion Our results suggest that circDGCR8, associated with atrial remodelling, holds potential as a predictive biomarker for both AF progression and post-ablation recurrence.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"35 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920207","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":"Plasma proteomic and metabolomic profiling of coronary and carotid atherosclerosis in the SCAPIS study - differences and similarities.","authors":"Tove Fall,Anders Gummesson,Ulf Hammar,Håkan Ahlström,Oskar Angerås,Anders Blomberg,John Brandberg,Kenneth Caidahl,Elin Chorell,Jan E Engvall,Per Eriksson,David Erlinge,Bruna Gigante,Ola Hjelmgren,Johan Hultdin,Tomas Jernberg,Johan Kihlberg,Lars Lind,Martin Magnusson,Fredrik H Nyström,Carlo Pirazzi,Alexandru Schiopu,Johan Sundström,Stefan Söderberg,Carl Johan Östgren,Gunnar Engström","doi":"10.1093/cvr/cvaf076","DOIUrl":"https://doi.org/10.1093/cvr/cvaf076","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"13 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915031","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":"Harnessing the power of the brain to fight metabolic diseases.","authors":"Emiel P C van der Vorst,Giuseppe Lembo","doi":"10.1093/cvr/cvaf061","DOIUrl":"https://doi.org/10.1093/cvr/cvaf061","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"115 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914868","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":"The three calmodulin genes - territories defined?","authors":"Marcos Gonzalez,Quang-Kim Tran","doi":"10.1093/cvr/cvaf075","DOIUrl":"https://doi.org/10.1093/cvr/cvaf075","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"23 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903086","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":"Abdominal aortic aneurysm histomorphology shows different inflammatory aspects among patients and is not associated with classic risk factors – the HistAAA study","authors":"Maja Carina Nackenhorst, Felix Menges, Bianca Bohmann, David Zschäpitz, Christine Bollwein, Sven Flemming, Nadja Sachs, Wolf Eilenberg, Christine Brostjan, Christoph Neumayer, Matthias Trenner, Wiebke Ibing, Hubert Schelzig, Christian Reeps, Lars Maegdefessel, Heinz Regele, Markus Udo Wagenhäuser, Claus Jürgen Scholz, Thomas Christian Gasser, Albert Busch","doi":"10.1093/cvr/cvaf071","DOIUrl":"https://doi.org/10.1093/cvr/cvaf071","url":null,"abstract":"Text Abstract Aims Abdominal aortic aneurysm (AAA) treatment is upon a diameter threshold. Attempts for medical growth abrogation have failed thus far. This study aims to elucidate the heterogeneity of AAA histomorphology in correlation to individual patient and aneurysm metrics. Methods and Results Samples from the left anterior aneurysm wall underwent histologic analysis including angiogenesis, calcification, fibrosis, type and grade of inflammation in adventitia and media. Clinical information and state of aneurysm (intact, symptomatic, ruptured, inflammatory) were retrieved. Semi-automated geometric analysis (Endosize©, Therenva) and finite element methods (A4Clinics© Research Edition, Vascops GmbH) were included. 364 patients’ samples (85.4% male, median age 69 years) were scored for acute or chronic inflammation, both not associated with rupture (52x), symptomatic disease (37x) or diameter (57 [52-69] mm; p = 0.87). The degree of fibrosis and the presence of angiogenesis were significantly higher (both p < 0.001) with increasing inflammation, which in turn significantly decreased with patient age (est = - 0.015/year, p = 0.017). No significant differences were seen for acute (vs. elective), male (vs. female) or diabetic patients. Aneurysm geometry (n=252) or annual growth rate (n=142) were not associated with histologic characteristics. Yet, local luminal thrombus formation was significantly higher with increasing inflammation (p = 0.04). Conclusion Type and degree of inflammation are the most distinguishable histologic characteristics in the AAA wall between individual patients, yet are not associated with diameter or rupture. Local luminal thrombus formation is associated with inflammatory features and suggests a vivid bio-physical compartment with intra-individual age-dependent differences.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"140 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884693","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":"Distinct intracellular spatiotemporal expression of Calmodulin genes underlies functional diversity of CaM-dependent signaling in cardiac myocytes","authors":"Vladimir Bogdanov, Juan I E Mariangelo, Andrew M Soltisz, Galina Sakuta, Anastasia Pokrass, Casey Beard, Benjamin Hernandez Orengo, Roman Kalinin, Ali Ulker, Bennett Yunker, Svetlana Tikunova, Jenna Thuma, Xianyao Xu, Thomas J Hund, Rengasayee Veeraraghavan, Jonathan P Davis, Sandor Györke","doi":"10.1093/cvr/cvaf059","DOIUrl":"https://doi.org/10.1093/cvr/cvaf059","url":null,"abstract":"Aims This study aims to resolve the mechanisms underlying Calmodulin (CaM)'s signaling diversity by investigating whether the three CaM genes—Calm1, Calm2, and Calm3—play distinct or redundant roles in cardiac myocytes, focusing on their spatial mRNA localization and interactions with key targets. Methods and Results We utilized single-molecule mRNA detection and 3D imaging to map the spatial distribution of Calm1, Calm2, and Calm3 mRNAs within ventricular myocytes. These mRNAs were found to be consistently positioned within specific cellular zones, overlapping with their target mRNAs and forming region-specific transcript conjunctions. This spatial organization aligns with two distinct protein synthesis pathways: centralized synthesis near the nucleus for proteins such as Cx43 and localized synthesis in more peripheral cytosolic areas for proteins like RyR2. Ablation of Calm1 triggered compensatory increases in Calm2 and Calm3; however, this compensation was insufficient to restore normal CaM transcript distribution, leading to disrupted Ca²⁺ handling. In the context of hypertrophic heart failure (HF), the distribution and spatial interactions of CaM transcripts, while potentially adaptive to support myocyte growth, become disrupted, leading to disorganized CaM signaling. Conclusion Our findings reveal that Calm1, Calm2, and Calm3 fulfill distinct, non-redundant roles in cardiac myocytes through their spatially regulated mRNA localization (spatiotemporal coding). This precise spatial control of mRNA localization is critical for region-specific CaM signaling and is disrupted in hypertrophic heart failure, contributing to pathological remodeling.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"2 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872645","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 new protein isoform encoded by human circular RNA circSLC8a1 contributes to cardiac remodeling","authors":"Feiya Li, William W Du, Xiangmin Li, Shuoyang Wen, Jindong Xu, Qiwei Yang, Jinfeng Wei, Sheng Wang, Nan Wu, Javeria Qadir, Burton B Yang","doi":"10.1093/cvr/cvaf058","DOIUrl":"https://doi.org/10.1093/cvr/cvaf058","url":null,"abstract":"Aims Circular RNA circSLC8a1 has been previously suggested to possess translation potential, but experimental evidence supporting this notion has been lacking. We aim to understand the functions of circSLC8a1 and its translated protein in cardiac remodeling. Methods and Results To elucidate the functional significance of circSLC8a1, we established a transgenic mouse line expressing circSLC8a1 and its translated protein SLC8a1-604. We present compelling evidence confirming the translation potential of circSLC8a1 (hsa_circ_0005232) both in vitro and in vivo. The back-splicing event within hsa_circ_0005232 leads to the generation of a novel circRNA-derived protein comprising 604 amino acids, named SLC8a1-604, which has not been previously reported. These SLC8a1-604 transgenic mice exhibited a heart failure phenotype. In further investigations, we induced pressure overload in the transgenic mice, revealing a significant decrease in heart function compared to litter-matched negative controls. Notably, our findings indicate that the reduced heart function observed in the transgenic mice can be attributed to the presence of the circRNA-translated protein, SLC8a1-604, rather than the circRNA itself. Mechanistically, we found that SLC8a1-604 translocated into mitochondria, where it exerted its effects by binding to POLRMT. This interaction results in a downregulation of mitochondrial gene transcription, leading to a decrease in ATP synthesis. Conclusion Our study provides evidence that circSLC8a1 has the capacity to encode a novel protein isoform, SLC8a1-604, which plays a pivotal role in the regulation of heart functions: circSLC8a1 modulates the remodeling process of cardiac pressure overload by translating into a functional protein. Translational Perspective This proof-of-concept study may lay the foundation for potential clinical applications in circular RNA therapy.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"17 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872648","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":"Sex and sex hormonal regulation of the atrial inward rectifier potassium current (IK1): insights into potential pro-arrhythmic mechanisms.","authors":"Lucilla Giammarino,Lluis Matas,Nicolò Alerni,András Horváth,Varjany Vashanthakumar,Saranda Nimani,Miriam Barbieri,Sahej Bains,Ruben Lopez,Julien Louradour,Balazs Ördög,Thomas Hof,Ange Maguy,Giulio Conte,Angelo Auricchio,Ulrich Schotten,Katja E Odening","doi":"10.1093/cvr/cvaf074","DOIUrl":"https://doi.org/10.1093/cvr/cvaf074","url":null,"abstract":"AIMSPronounced sex-differences are known in the incidence of atrial fibrillation (AF). In this study, we aimed to investigate the atrial electrophysiological properties that may underlie sex-differences in AF incidence in the younger population, focusing on IK1, a cardiac ion current important for action potential (AP) stability and triggered activity.METHODS AND RESULTSWe assessed sex-differences in P-wave morphology in 12-lead ECG in healthy young New Zealand White rabbits. Males presented longer P-wave duration and larger P-wave area compared to females. Patch-clamp experiments were performed in isolated rabbit atrial cardiomyocytes (CMs). Male atrial CMs presented higher DAD incidence, amplitude, and area under the curve (AUC) than females, potentially facilitating the presence of atrial triggered activity in males. Male atrial CMs showed a less hyperpolarized resting membrane potential (RMP), a 50% smaller IK1, and a 26% reduction in Kir2.1 protein expression, a pore forming subunit of IK1, than females. Dihydrotestosterone (DHT) effects were investigated acutely and semi-chronically ex vivo. Experiments showed that the sex-difference in IK1 could be mimicked by DHT. In female atrial CMs, acute and semi-chronic (24h) DHT administration reduced IK1. In the presence of a PKC-inhibitor, DHT-mediated IK1 reduction was not observed in atrial female CMs, suggesting it to be PKC-mediated. Chronic DHT-effects were investigated in vivo in female rabbits after hormone-releasing pellet implantation. After two weeks, animals showed a significantly prolonged and larger P-wave, a smaller atrial IK1 and a trend towards an increased DAD amplitude and AUC.CONCLUSIONSSex impacts on atrial electrophysiology, leading to sex-differences in P-wave morphology, triggered activity, RMP, and IK1. These sex-differences can be mimicked by sex hormone-treatment, suggesting that sex hormones ‒ particularly DHT ‒ play a pivotal role in mediating sex-differences in atrial electrophysiology. Such sex-differences might impact on the propensity to develop AF, particularly in the younger population.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"5 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871983","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":"Identification of pulmonary artery stiffening due to left heart disease by ultrasonography","authors":"Mariya M Kucherenko, Marian Kukucka, Pengchao Sang, Niklas Hegemann, Qiuhua Li, Felix Hennig, Ruhi Yeter, Tara Gransar, Alexander Mladenow, Anna Emmerich, Andrea Orsenigo, Jana Grune, Volkmar Falk, Wolfgang M Kuebler, Christoph Knosalla","doi":"10.1093/cvr/cvaf066","DOIUrl":"https://doi.org/10.1093/cvr/cvaf066","url":null,"abstract":"Aims Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) that leads to right heart failure and death. Pulmonary artery (PA) stiffening has recently emerged as an important diagnostic and prognostic parameter in PH. The present study aimed to develop and validate an ultrasonographic index to identify PA stiffening in PH due to left heart disease (PH-LHD). Methods and Results First, ultrasonographic stiffness index (US-SI) was derived from pulmonary arterial (PA) radial strain (PA-RS), diameter, and stroke volume in rat model, and correlated to ex vivo measured “true” PA stiffness E. Then, US-SI was validated in a cohort of 24 LHD patients with or without PH prior to heart transplantation and again compared to “true” PA stiffness measured ex vivo in collected PA specimens. In rats, ultrasonographic PA-RS and US-SI correlated closely with E, and both were able to detect “true” PA stiffening with ≥ 80% sensitivity and specificity. In LHD patients, even though ultrasonographic right PA radial strain (rPA-RS) or US-SI correlated similarly with E, observer assessment and testing for diagnostic validity identified US-SI as more robust and accurate method that detects “true” PA stiffening with 83.3% sensitivity and 95.8% specificity. Conclusion(s) Both PA strain and US-SI allow for ultrasonographic detection of PA stiffening in patients or animal models with LHD, however, US-SI identifies patients with stiffened PA with higher diagnostic validity and accuracy. Translational Perspective Clinical implementation of US-SI may improve risk stratification in LHD patients and longitudinal monitoring of progression or treatment efficiency in PH-LHD. The animal-to-beside approach used in this study may promote the rapid translation of bio- and pathomechanical insights between the clinical and preclinical scenarios.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872649","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":"Unravelling inflammation: the critical role of ETS2 in macrophage activation and chronic disease.","authors":"Soumaya Ben-Aicha,Gustavo Ramos","doi":"10.1093/cvr/cvaf072","DOIUrl":"https://doi.org/10.1093/cvr/cvaf072","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"33 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871968","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}