Cardiovascular Research最新文献

{"title":"Assessing pulmonary artery stiffening with ultrasonography: a step forward for the assessment of PH due to left heart disease?","authors":"Merve Keles, Allan Lawrie","doi":"10.1093/cvr/cvaf122","DOIUrl":"https://doi.org/10.1093/cvr/cvaf122","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564620","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":"From lipids and inflammation to artificial intelligence-driven therapeutics: the 93rd European atherosclerosis society (EAS) congress 2025 in focus.","authors":"Danila Gurgone,Jeffrey Kroon,Charalambos Antoniades","doi":"10.1093/cvr/cvaf110","DOIUrl":"https://doi.org/10.1093/cvr/cvaf110","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"20 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547776","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":"Effect of trimetazidine dihydrochloride therapy on myocardial external efficiency in preclinical individuals with a hypertrophic cardiomyopathy pathogenic variant: results of the ENERGY trial","authors":"Beau Olivier van Driel, Stephan A C Schoonvelde, Sonia Borodzicz-Jazdzyk, Roy Huurman, Julia Visch, Lourens Robbers, Hans Harms, Judith Verhagen, Alexa Vermeer, Joost van den Aardweg, Albert C van Rossum, Tjeerd Germans, Michelle Michels, Jolanda van der Velden","doi":"10.1093/cvr/cvaf120","DOIUrl":"https://doi.org/10.1093/cvr/cvaf120","url":null,"abstract":"Aims Previous studies have shown that individuals with a hypertrophic cardiomyopathy (HCM) pathogenic variant (PV) or likely pathogenic variant (LPV) without a HCM phenotype (PV/LPV carrier) have decreased myocardial external efficiency (MEE), which is thought to be a key pathomechanism in the onset and progression of HCM. Metabolic treatments improved exercise capacity in HCM patients, but evidence that such drugs correct reduced MEE is lacking. The ENERGY trial is a double-blind, placebo-controlled randomized clinical trial to define if the metabolic drug trimetazidine (TMZ) corrects reduced MEE in PV/LPV carriers for HCM. Methods and results 51 MYBPC3 or MYH7 PV/LPV carriers were screened after which 40 were included and randomized into a treatment group (n=20) or placebo group (n=20) stratified for sex. Participants were treated with TMZ 20mg or placebo three times daily during eight weeks. The main outcome of this study was MEE as measured by [11C]-acetate positron emission tomography/computed tomography (PET/CT) and cardiac magnetic resonance (CMR) scan. Secondary outcomes were exercise parameters as measured by cardio-pulmonary exercise testing (CPET). Drug safety was monitored by (serious) adverse event registration. Treatment groups were comparable in terms of age, sex, body mass index, P/LP gene variant, and echocardiographic parameters without significant differences. Baseline CMR parameters and MEE were not significantly different between treatment groups. Eight weeks of treatment with TMZ did not significantly alter MEE compared to placebo. The mean MEE changed from 30.3±3.8 to 29.8±4.3 percent in the placebo group and from 30.1±4 to 29.1±4 percent in the TMZ group. Compared to placebo, the TMZ group did not have a significantly different MEE (difference -0.44, 95% interaction CI, -2.863 to 1.986, P=0.68). The mean V’O2max as a percentage of predicted V’O2max (V’O2max %pred) changed from 108±17 to 111±19 (95% CI, -6 to 10, P=0.84) percent in the placebo group and from 105±17 to 113±14 (95% CI, 1 to 16, P=0.03) percent in the TMZ group. After adjustment for baseline, the TMZ group had a significantly increased V’O2max %pred (difference 6.37, 95% interaction CI, -3 to 16, P=0.04). Conclusion The ENERGY trial is the first proof-of-concept randomized controlled trial to test the hypothesis that TMZ improves MEE in MYBPC3 or MYH7 PV/LPV carriers. We conclude that metabolic therapy with TMZ may not correct the P/LP gene variant-related decrease in MEE. Trial registration Netherlands Trial Register NL7492 (URL https://onderzoekmetmensen.nl/nl/trial/25078)","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"71 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547191","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":"Women in cardiology: how to meet European Society of Cardiology gender policy.","authors":"Agnieszka Tycinska,Jaroslaw Drozdz,Anna Fijalowska,Renata Glowczynska,Agnieszka Gorgon-Komor,Marcin Kurzyna,Katarzyna Mizia-Stec,Agnieszka Pawlak,Janina Stepinska,Piotr Szymanski,Agnieszka Wolczenko,Robert Zymlinski","doi":"10.1093/cvr/cvaf107","DOIUrl":"https://doi.org/10.1093/cvr/cvaf107","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"19 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521343","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":"Deciphering metabolic reprogramming in atherosclerosis through a multi-omics approach.","authors":"Pascal Azar, Marie-Luce Bochaton-Piallat","doi":"10.1093/cvr/cvaf114","DOIUrl":"https://doi.org/10.1093/cvr/cvaf114","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511607","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":"Fetuin-A increases thrombosis risk in non-alcoholic fatty liver disease by binding to TLR-4 on platelets","authors":"Peng Zhang, Zhiyong Qi, Huajie Xu, Luning Zhou, Xin Zhao, Haoxuan Zhong, Wenxuan Zhou, Bing Fan, Hongyi Wu, Junbo Ge","doi":"10.1093/cvr/cvaf096","DOIUrl":"https://doi.org/10.1093/cvr/cvaf096","url":null,"abstract":"Aims Fetuin-A, a liver-derived heterodimeric plasma glycoprotein, exhibits abnormal elevation in non-alcoholic fatty liver disease (NAFLD). Plasma fetuin-A levels correlate closely with both morbidity and mortality associated with cardiovascular diseases. However, the precise influence of fetuin-A on NAFLD-related platelet activation and thrombosis remains to be elucidated. Methods and results Fetuin-A directly amplified agonist-induced platelet aggregation, dense granule adenosine triphosphate release, P-selectin exposure, integrin αIIbβ3 activation, spreading, and clot retraction. Mechanistically, fetuin-A bound to platelet Toll-like receptor-4 (TLR-4), activating TLR-4/MyD88, SFK/PI3 K/AKT, cGMP/PKG, and mitogen-activated protein kinase signalling pathways to enhance platelet activation. TLR-4 specific antagonist TAK-242 and TLR-4-deficient mice confirmed the TLR-4 dependence of these effects. Oral administration of firsocostat, rosuvastatin, or pioglitazone demonstrated efficacy in alleviating thrombosis formation in NAFLD mice by reducing fetuin-A levels and attenuating platelet hyperreactivity. Notably, the fetuin-A-inhibiting antibody potently suppressed platelet activation and inhibited thrombosis formation in NAFLD mice. Administration of this antibody attenuated thromboembolism and microvascular thrombosis in NAFLD mice, thereby safeguarding the lung, heart, and brain from exacerbated tissue infarcts. Finally, a positive correlation between plasma fetuin-A concentration and platelet aggregation was observed in NAFLD patients. Conclusion Fetuin-A emerges as a positive regulator of platelet hyperreactivity in NAFLD. Acting via TLR-4-dependent signalling pathways, plasma fetuin-A directly amplifies platelet activation and promotes in vivo thrombosis. Firsocostat, rosuvastatin, and pioglitazone abrogate these enhancing effects by reducing fetuin-A levels. The fetuin-A-inhibiting antibody presents potential therapeutic advantages to prevent thrombotic complications in NAFLD.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"22 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503539","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":"Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischaemic stroke","authors":"Jordan J Lee, Hiran A Prag, Karthik Chary, Jiro Abe, Shinpei Uno, Annabel Sorby-Adams, Chak Shun Yu, Olga Sauchanka, Amin Mottahedin, Joshua D Kaggie, Ferdia A Gallagher, Michael P Murphy, Thomas Krieg","doi":"10.1093/cvr/cvaf118","DOIUrl":"https://doi.org/10.1093/cvr/cvaf118","url":null,"abstract":"Aims Ischaemic stroke is increasingly treated by mechanical thrombectomy (MT) with the more rapid and complete reperfusion of the ischaemic tissue enhancing patient outcome, compared to recombinant tissue plasminogen activator (rtPA) alone. Even so, there is still extensive brain infarction and disability following MT, that is exacerbated by ischaemia-reperfusion injury (IRI) and other pathological processes during reperfusion. Hence, an adjunct therapy to MT that decreases IRI should enhance patient outcomes. Methods and Results To test this possibility, we adapted the transient middle cerebral artery occlusion (tMCAO) mouse model to allow local intra-arterial administration of acidified disodium malonate (aDSM) to decrease IRI as the ischaemic tissue was reperfused. Administration of aDSM (160 mg/kg; pH 6) during reperfusion decreased brain infarct volume by ∼60 % when assessed by magnetic resonance imaging (MRI) 24 h after reperfusion and improved neurological function. Conclusion These findings suggest aDSM as a potential adjunct therapy to further improve outcomes for stroke patients treated by MT.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"17 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503528","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":"Delineation of a thrombin receptor-stimulated vascular smooth muscle cell transition generating cells in the plaque-stabilising fibrous cap","authors":"James C K Taylor, Matthew D Worssam, Sebnem Oc, Jordi Lambert, Krishnaa T Mahbubani, Kirsty Foote, Allie Finigan, Yee-Hung Chan, Nichola Figg, Murray C H Clarke, Martin R Bennett, Helle F Jørgensen","doi":"10.1093/cvr/cvaf112","DOIUrl":"https://doi.org/10.1093/cvr/cvaf112","url":null,"abstract":"Aims Vascular smooth muscle cells (VSMCs) accumulate in atherosclerotic plaques and exhibit remarkable phenotypic plasticity, contributing to both plaque growth and stability. The plaque-stabilising fibrous cap is rich in VSMC-derived cells, yet the cellular transitions and regulatory mechanisms governing fibrous cap formation remain unclear. Here, we aimed to identify the VSMC phenotypic transitions associated with this critical process. Methods and Results Mapping of lineage-traced VSMCs during plaque development revealed investment of VSMCs prior to fibrous cap formation. Using single-cell RNA-sequencing (scRNA-seq) profiles of lineage-traced VSMCs from atherosclerotic and acutely injured mouse arteries, we identified a disease-specific VSMC state co-expressing contractile genes with extracellular matrix (ECM) components (including fibrillar collagens and elastin) and NOTCH3, which are associated with fibrous cap formation. Computational trajectory analysis predicted that this proposed fibrous cap-related VSMC (fcVSMC) state arises from a previously described plastic, intermediate VSMC population expressing SCA1 and VCAM1. Clonal analysis further showed that NOTCH3+ fcVSMCs derive from intermediate VSMCs in both atherosclerosis and an acute vascular injury model, suggesting a conserved disease-relevant mechanism. The fcVSMCs were enriched in plaque fibrous caps compared to lesion cores, consistent with a role in fibrous cap formation. By combining scRNA-seq trajectory analysis and spatial transcriptomics of human atherosclerotic plaques, we identified protease-activated receptor-1 (PAR1) as a candidate regulator of fcVSMC generation. PAR1 was expressed by VSMCs in human plaque fibrous caps and PAR1 activation by thrombin induced expression of contractile genes and ECM components associated with the fcVSMC state in human VSMCs. Conclusions Our findings identify a VSMC transition linked to fibrous cap formation in atherosclerosis and show this is modelled by vascular injury. We identify VSMC-expressed PAR1 as a potential therapeutic target for promoting plaque stability by driving the transition to the matrix-producing, fibrous cap-associated VSMC state.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"70 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503529","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":"Systematic review and meta-analysis of respiratory viral triggers for acute myocardial infarction and stroke","authors":"Tu Q Nguyen, Diana Vlasenko, Aishwarya N Shetty, Eric Zhao, Christopher M Reid, Hazel J Clothier, Jim P Buttery","doi":"10.1093/cvr/cvaf092","DOIUrl":"https://doi.org/10.1093/cvr/cvaf092","url":null,"abstract":"Respiratory viral infections may trigger acute cardiovascular events. However, relative pathogen-specific associations are poorly understood, limiting optimal preventive recommendations. The aim of this study was to systematically review the association between respiratory viruses with two primary outcomes, acute myocardial infarction (AMI) and stroke. We searched MEDLINE, PubMed, Embase, Cochrane, and Web of Science, from database inception to 26 August 2024. Analytical epidemiological studies of respiratory viruses identified by laboratory-confirmatory testing, involving human participants of any age in any country, were eligible for inclusion. Risk of bias was assessed using the Cochrane Collaboration approach. Data from studies of sufficient quality and homogeneity were pooled using a random-effects model. Certainty of the evidence was assessed for each identified viral trigger. Of 11 017 articles identified, we included a total of 48 studies published between 1978 and 2024. All were observational studies, of which 28 were suitable for quantitative synthesis. There was moderate-certainty evidence that influenza triggers AMI (incidence rate ratio, 5.37; 95% CI, 3.48–8.28; I2 = 69.4%). We found high-certainty evidence that influenza triggers stroke—influenza was associated with a 4.7-fold increased risk of stroke within the first 28 days following infection (incidence rate ratio, 4.72; 95% CI, 3.78–5.90; I2 = 0%). SARS-CoV-2 and cytomegalovirus may trigger stroke, while SARS-CoV-2, respiratory syncytial virus, and Coxsackie B were also identified as potential triggers for AMI. In this systematic review and meta-analysis, the findings suggest that common, often vaccine-preventable, respiratory viral infections are associated with an increased risk of acute cardiovascular events.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"630 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500618","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 role of uremic toxin indoxyl sulfate in the pathophysiology of aortic valve stenosis","authors":"Philip Düsing, Isabel Göbel, Ansgar Ackerschott, Laurine Reese, Patrick Giavalisco, Frederik Dethloff, Sven Thomas Niepmann, Marta Stei, Thomas Beiert, Sebastian Zimmer, Christian Kurts, Georg Nickenig, Felix Jansen, Andreas Zietzer","doi":"10.1093/cvr/cvaf106","DOIUrl":"https://doi.org/10.1093/cvr/cvaf106","url":null,"abstract":"Aims Chronic kidney disease (CKD) is closely associated with cardiovascular disease (CVD). This includes aortic valve stenosis (AS), one of the most common valve diseases among adults. CKD leads to the retention of uremic toxins such as indoxyl sulfate (IS), which is known to induce inflammatory and pro-calcific processes. We hypothesise that IS specifically induces AS formation. Methods and Results Stimulation of human valvular interstitial cells (VICs) with IS in addition to phosphate led to increased calcification. RNA sequencing identified naked cuticle homolog 2 (NKD2) as an upregulated gene in VICs under uremic conditions. Knockdown of NKD2 reduced calcification of VICs and upregulation of IL-6. The organic anion transporting polypeptide 3A1 (OAT3A1) was identified to mediate IS uptake as well as upregulation of NKD2 and IL-6. We identified NF-κB signalling to be involved in IS-induced IL-6 upregulation. In vivo, we investigated combined models of adenine-induced kidney injury or oral IS supplementation with wire injury-induced AS in C57BL/6J mice. Echocardiography showed aggravated AS in uremic mice compared to control mice after wire injury. Explanted valves from uremic mice with AS exhibited a significant increase in macrophage infiltration, fibrotic areas and valvular NKD2 expression compared to controls. IS-treated mice showed aggravated AS compared to control mice. This was accompanied by more prominent valve fibrosis, macrophage infiltration, and NKD2 expression in explanted valves of IS-treated mice. In the blood and bone marrow, IS treatment led to the differentiation of monocytes into intermediate and non-classical monocytes. This was paralleled by IS-induced monocyte adhesion to valvular endothelial cells in vitro. Conclusion Uremic conditions aggravate AS development in mice by inducing valvular fibrosis and macrophage infiltration. Indoxyl sulfate is involved in this process and stimulates monocyte differentiation and adhesion to the valvular endothelium. On a cellular level, we hypothesize that IS-mediated NKD2 induction leads to a calcifying and inflammatory response in VICs.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"46 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500627","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}