Cardiovascular Research最新文献

{"title":"Complex relationship between iron status and outcomes of STEMI: hypothesis-generating study","authors":"M Vera-Aviles, S N Kabir, M D Christodoulou, G Mohammad, M Shanmuganathan, R Kotronias, J G F Cleland, K M Channon, S Lakhal-Littleton","doi":"10.1093/cvr/cvag223","DOIUrl":"https://doi.org/10.1093/cvr/cvag223","url":null,"abstract":"Aims Iron deficiency (ID) is common amongst patients with ST-elevation myocardial infarction (STEMI). Its impact on outcomes remains contested. Previous studies reported favourable or adverse impacts depending on outcome measures, sampling timepoints, ID definition and follow-up duration. This study systematically characterises the prognostic impact of iron status on short-term, mid-term and long-term outcomes, and evaluates the effect of sampling timepoint and ID definition on these prognostic relationships. Methods & Results We performed an observational cohort study in patients with acute STEMI (n = 167) and no prior heart failure (HF). Iron markers were sampled at presentation, and successive timepoints thereafter. Cardiac Magnetic Resonance was performed at 2 days and 6 months. Major adverse cardiovascular events (MACE), consisting of new-onset HF, recurrent MI or cardiac death were recorded over 4.5 years. Mechanisms were evaluated in a preclinical model of MI. ID was common at presentation, affecting between 44.9% and 67%, depending on ID definition. Tsat <20%, serum iron<13μM, or European Society of Cardiology’s definition, but not ferritin<100μg/L, independently predicted lower risk of MACE. Lower Tsat at presentation predicted attenuated infarct and non-infarct T1, and smaller left ventricular volumes at 2 days. This prognostic effect was weakened by delayed sampling. Lower Tsat and serum iron in the post-acute timepoints, but not at presentation, predicted lower myocardial salvage at 6 months. In mice, MI triggered an acute myocardial labile iron storm and early LV remodelling, progressing to HF. Baseline ID and acute iron chelation averted these effects. Conclusions This study gives rise to the hypothesis that ID at presentation with STEMI improves long-term outcomes by attenuating myocardial injury. It reconciles previous conflicting reports by revealing the confounding effects of delayed sampling, and non-interchangeability of different ID definitions. It suggests iron chelation in the acute stage, followed by post-acute iron repletion might improve long-term outcomes.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"3 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218776","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 to letter \"reassessing safety signals in low-dose thrombolysis for intermediate-high-risk pulmonary embolism\".","authors":"J Kjaergaard, L E Bang, M K Ersbøll, J Carlsen","doi":"10.1093/cvr/cvag208","DOIUrl":"10.1093/cvr/cvag208","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206561","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":"CD34+ myofibroblasts promote neointima formation in vein grafts by activating ferroptosis-induced smooth muscle cell phenotype switch.","authors":"Simon S Xu, Han Wang, Pengwei Zhu, Li Qiao, Xiaodong Xu, Kai Chen, Ashish Patel, Xiaoping Yang, Yunpeng Bai, Xiaoshen Hu, Qingbo Xu, Alberto Smith, Qingzhong Xiao, Bijan Modarai","doi":"10.1093/cvr/cvag235","DOIUrl":"https://doi.org/10.1093/cvr/cvag235","url":null,"abstract":"<p><strong>Aim: </strong>Vein graft (VG) failure due to adverse remodeling and aggressive neointimal hyperplasia is a major complication and key limiting factor for maintaining long-term VG patency. CD34+ cells have been implicated in multiple cardiovascular diseases, but their functional involvements and contributions to VG failure remain elusive. In this study, we aimed to investigate the functional role of CD34+ cells in VG pathogenesis.</p><p><strong>Methods and result: </strong>Single cell RNA sequencing (scRNA-seq) analysis was conducted to uncover cellular heterogeneity of normal healthy and grafted veins as well as CD34+ cells in VGs. Genetic lineage tracing and depletion strategies were applied to delineate the functional involvements and potential contributions of CD34+ cells to VG remodeling. Multiple functional and biochemistry assays were conducted to identify and elucidate the key signal pathways underpinning smooth muscle cell (SMC) ferroptosis and phenotype switching.A total of 22,213 cells from normal healthy and grafted veins were included in scRNA-seq analysis, which showed a heterogeneous population of CD34+ cells as well as activated ferroptosis pathways and SMC phenotypic alterations in VGs. Using the inducible lineage tracing Cd34-CreERT2;R26-tdTomato mouse model, we showed that CD34+ cells were mainly differentiated into fibroblasts in VGs. Depletion of CD34+/Postn+ myofibroblasts in a triple transgenic (Cd34-Dre;Postn-CreERT2;Dou-tdT-DTR) mouse model significantly decreased VG-induced neointimal hyperplasia. Cellular communication analysis identified Jagged 1/Notch3 (neurogenic locus notch homolog protein 3) as the most upregulated signaling axis between CD34+ cell-derived fibroblasts and SMCs. Notch3 activation in SMCs by CD34+ cell-derived fibroblasts promoted SMC ferroptosis and switching to a synthetic/secretory phenotype in VGs. Blocking Jagged1 and Notch3 signalling as well as inhibition of ferroptosis attenuated vascular adverse remodeling and neointimal hyperplasia in VGs.</p><p><strong>Conclusions: </strong>This study provides a transcriptional and cellular landscape in normal healthy and grafted veins and shows that heterogeneous CD34+ cells serve as a key contributor to vascular remodeling and neointimal hyperplasia in VGs. We also demonstrate that CD34+ cell-derived myofibroblasts promote neointimal hyperplasia through Jagged1/Notch3 signal axis, suggesting that blocking Jagged1/Notch3 activation or inhibiting ferroptosis may provide a novel approach to prevent VG failure.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179578","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":"Methods first, interpretation last.","authors":"Meihan Guo, Xinyu Liu, Zihao Huang, David Montero","doi":"10.1093/cvr/cvag229","DOIUrl":"https://doi.org/10.1093/cvr/cvag229","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179616","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":"Physically interacting immune cells in cardiometabolic disease: established platelet-immune aggregates and emerging leukocyte-leukocyte complexes","authors":"Naome Mwesigwa, Annet Kirabo, Celestine N Wanjalla","doi":"10.1093/cvr/cvag231","DOIUrl":"https://doi.org/10.1093/cvr/cvag231","url":null,"abstract":"Chronic immune activation contributes to cardiometabolic disease and has most often been attributed to soluble mediators or changes in individual immune-cell subsets. A complementary dimension of immune organization is captured by direct physical interactions between immune cells, detected in blood or dissociated samples. While most dual-lineage flow-cytometric events should still be excluded as technical doublets, a validated subset represents true cell-cell conjugates (i.e., physically interacting immune cells rather than antibody-antigen complexes). The evidence base, however, is uneven as platelet-leukocyte aggregates are well-established biomarkers of platelet activation and thromboinflammation, while circulating non-platelet immune cell-cell complexes, particularly T cell-monocyte complexes, remain an emerging field supported by relatively few primary studies. Across acute infection and vaccination, these complexes appear regulated and may reflect coordinated immune activation. In chronic inflammatory states, including HIV and metabolic dysfunction, persistent complexes have been associated with inflammation and cardiometabolic risk, although mechanistic and causal data remain limited. Here, we review the current evidence for circulating immune cell complexes, distinguish established platelet-containing aggregates from the nascent literature on other immune-cell pairings, discuss candidate mechanisms that may support their formation and persistence, outline methodological requirements for their study, and consider their potential as biomarkers and therapeutic-response tools in cardiometabolic disease.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"49 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149152558","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":"Inflammation meets calcium in iCMP.","authors":"Akshay Ware, Sameen Fatima, Wesley T Abplanalp","doi":"10.1093/cvr/cvag108","DOIUrl":"10.1093/cvr/cvag108","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1891-1893"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004836","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":"Autonomous 0.3-Hz breathing causes slow 0.1-Hz brain-heart oscillations in humans.","authors":"Gert Pfurtscheller, Maciej Kaminski, Beate Rassler, Wolfgang Klimesch, Gerhard Schwarz, Klaus Pfurtscheller, Gaetano Valenza","doi":"10.1093/cvr/cvag164","DOIUrl":"10.1093/cvr/cvag164","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1894-1896"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590578","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":"PKP2 orchestrates OXPHOS expression in cardiomyocytes via a PGC1α-dependent mechanism.","authors":"Su Ji Han, Daphne van den Berg, Hesther de Ruiter, Hoyee Tsui, Eirini Kyriakopoulou, Tim Koopmans, Ilaria Perini, Jantine Monshouwer-Kloots, Sebastiaan J van Kampen, Anneline S J M Te Riele, Ilse R Kelters, Monica Gianoli, Boudewijn M T Burgering, Eva van Rooij","doi":"10.1093/cvr/cvag141","DOIUrl":"https://doi.org/10.1093/cvr/cvag141","url":null,"abstract":"<p><strong>Aims: </strong>Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiac disease in which most patients carry (likely) pathogenic variants in desmosomal genes, most commonly in plakophilin-2 (PKP2). While the genetic causes are well described, the molecular mechanisms driving disease progression-particularly in response to exercise-remain poorly understood.</p><p><strong>Methods and results: </strong>To investigate disease-driving pathways in ACM, we used PKP2 mutant human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from ACM patients. Transcriptomic profiling revealed consistent downregulation of oxidative phosphorylation (OXPHOS) genes in PKP2 mutant hiPSC-CMs, which was confirmed in explanted ACM hearts carrying PKP2 variants. Reduced expression of OXPHOS-related genes was associated with lower PPARGC1A expression and decreased mitochondrial spare capacity in PKP2 mutant hiPSC-CMs. The reduction in PPARGC1A expression appeared to result, at least in part, from decreased AMPKα protein levels, a known activator of PPARGC1A previously shown to localize at the intercalated disc, as PKP2 mutant cells failed to increase PPARGC1A expression following treatment with AICAR, an AMPK activator. To directly assess whether increasing PPARGC1A expression could compensate for this defect, we overexpressed PPARGC1A, which partially restored OXPHOS gene expression and improved contractility in PKP2 mutant cells.</p><p><strong>Conclusion: </strong>Our study identifies a novel transcriptional mechanism linking PKP2 loss to reduced mitochondrial function via decreased PGC1α signaling, partially through reduced AMPKα levels. Disruption of this axis reduces OXPHOS gene expression and mitochondrial function in PKP2 mutant hiPSC-CMs, potentially impairing the heart's ability to meet increased energy demands during stress, and offering a mechanistic explanation for the detrimental effects of exercise in ACM. Furthermore, these findings highlight PGC1α induction as a potential therapeutic strategy to restore OXPHOS gene expression and mitochondrial adaptability in ACM.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"122 14","pages":"2024-2038"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165231","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":"Inflammatory cytokines and immune signalling in heart failure: mechanisms, models, and emerging therapies.","authors":"Guiomar Mendieta, Gianluigi Pironti, Jasper Tromp, Lars H Lund","doi":"10.1093/cvr/cvag172","DOIUrl":"10.1093/cvr/cvag172","url":null,"abstract":"<p><p>Inflammation plays a central role in the pathophysiology of heart failure (HF), and contributes to disease progression, morbidity, and mortality. However, the relationships between inflammatory cytokines and different HF subtypes are complex, heterogeneous, and bidirectional. In this review, we examine inflammatory pathways, biomarker profiles, and comorbidities in HF with reduced, mildly reduced, and preserved ejection fraction and summarize evidence on the use of high-sensitivity C-reactive protein as a biomarker for systemic inflammation in HF. We provide insights into emerging methodologies for biomarker discovery in HF and discuss the use of animal models to elucidate underlying mechanisms and test potential treatment strategies. Finally, we provide an overview of the therapeutic landscape, touching on past challenges and future opportunities for the development of targeted anti-inflammatory therapies in HF.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1901-1921"},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721520","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":"Heart-to-kidney signal by extracellular vesicles promotes kidney injury in cardiorenal syndrome.","authors":"Morad Asadi, Carlos G Santos-Gallego, Maria Anastasiadou, Jakob Christoph Voran, Benedikt-Johannes Becker, Hunter W Korsmo, Jianhua Li, Juan Antonio Requena-Ibanez, Brian Fardman, Vasile Pavlov, Yansui Li, Gohar Mosoyan, Yasmine Ammi, Weibin Zhou, Chengguo Wei, Steve Coca, Yongjie Yang, Zhengzi Yi, Weijia Zhang, Kiyotake Ishikawa, Tarik Bozoglu, Vivette D'Agati, Juan Badimon, John C He, Gianluigi Condorelli, Christian Kupatt, Derk Frank, Lewis Kaufman","doi":"10.1093/cvr/cvag230","DOIUrl":"https://doi.org/10.1093/cvr/cvag230","url":null,"abstract":"<p><strong>Aims: </strong>Cardiorenal syndrome type-1 (CRS1), defined as acute kidney injury occurring in the setting of acute cardiac illness, is associated with substantial morbidity and mortality. Our objective was to determine whether extracellular vesicles (EVs) derived from the injured heart localize to the kidneys and contribute to renal injury in CRS1, and to elucidate mechanisms by which cardiac-derived EVs mediate kidney damage.</p><p><strong>Methods and results: </strong>Using cardiomyocyte-specific EV reporter mice, we characterized the release of cardiac-derived EVs and their biodistribution to the kidneys. Acute myocardial infarction increased circulating levels of these EVs and enhanced their uptake by proximal tubular epithelial cells. To directly assess their impact on the kidney, EVs derived from cardiomyocytes cultured under normoxic (N-EV) or hypoxic (H-EV) conditions were injected into the renal arteries of wild-type mice. H-EV, but not N-EV, induced proximal tubular epithelial cell injury and worsening of kidney function. To identify EV biomarkers, we performed proteomic profiling of cargo from N-EV and H-EV, and validated the muscle-specific protein TRIM72 as a biomarker of EVs originating from injured cardiomyocytes. In a porcine CRS1 model, plasma levels of TRIM72 positive-EVs were increased, and we demonstrate their delivery to the kidney. Similarly, in CRS1 patients, higher plasma levels of TRIM72-positive EVs correlated with the development of acute kidney injury. Mechanistically, uptake of H-EVs by proximal tubular epithelial cells induced transcription of lipogenic genes and caused lipid accumulation, whereas lipogenesis blockade protected these cells from H-EV-induced injury. We subsequently found that reduced expression of the transcription factor FOXO3 drove H-EV-induced transcriptomic reprogramming. H-EV cargo was enriched with specific Foxo3-targeting miRNAs, whose delivery promoted proximal tubular epithelial cell cytotoxicity, oxidative stress, and suppressed FOXO3 levels.</p><p><strong>Conclusions: </strong>Overall, this work demonstrates that a Foxo3-targeting miRNA heart-to-kidney signal mediated by injured cardiac-derived EVs contributes to kidney injury in CRS1.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147396","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}