Cardiovascular Research最新文献

{"title":"miR-100-5p modulates postprandial triglyceride response by targeting PCSK9","authors":"Amandine Vanduyse, Alexandre Motte, Carolina Neves, Rita Daclat, Sophie Galier, Olivier Bluteau, Clément Materne, Eric Frisdal, Hervé Durand, Philippe Giral, Joe-Elie Salem, Jean-Marc Lacorte, Cedric Le May, Wilfried Le Goff, Philippe Lesnik, Maryse Guerin","doi":"10.1093/cvr/cvag247","DOIUrl":"https://doi.org/10.1093/cvr/cvag247","url":null,"abstract":"Aims Elevated postprandial hypertriglyceridemia (PP-HTG) is a significant risk factor for development of cardiovascular diseases, however, the mechanisms underlying its exaggerated rise remains poorly understood. MicroRNAs (miRs) are known to be implicated in the regulation of lipid metabolism, thus identifying them as potential key players. We presently investigated whether miRs may control postprandial triglyceride (PP-TG) response. Methods and Results Postprandial changes in circulating miR expression as a function of the degree of postprandial TG response were evaluated in non-dyslipidemic healthy subjects (n = 32). The impact of miR-100-5p on hepatic gene expression was evaluated in differentiated Caco2 and HepG2 cells by analysis of hepatic transcriptome (RNAseq), western blot and ELISA. In vivo studies were conducted in C57BL/6J mice overexpressing mimic miR-100-5p. Postprandial variation in circ-miR-100-5p levels inversely correlate with PP-TG response. Cir-miR-100-5p was preferentially associated with TGRL particles of intestinal origin in subjects exhibited a low PP-TG response. Differential analysis of transcriptome from HepG2 cells transfected by either mimic miR-100-5p or scrambled mimic miR as control allowed us to identify PCSK9 as a down-regulated gene. Overexpression of miR-100-5p in HepG2 cells significantly decreased PCSK9 mRNA levels by 52% (p < 0.0001), cellular protein content by 28% (p < 0.0001) as well as PCSK9 secretion by 39% (p < 0.0001). In vivo systemic delivery of mimic miR-100-5p induced a two-fold reduction (p < 0.0001) on PP-TG in mice, such effect being abolished by blocking the circulating form of PCSK9 with alirocumab. Finally, we revealed a significant inverse relationship between circulating miR-100-5p expression levels and both PCSK9 levels and the magnitude of postprandial hypertriglyceridemia. Conclusion Taken together, our observations reveal that miR-100-5p regulates postprandial hypertriglyceridemia by targeting PCSK9, thus enhancing hepatic TGRL uptake. Our findings allow us to propose circ-miR-100-5p as a potential biomarker for early identification of subjects at high cardiovascular risk, prior to appearance of classical clinical features of metabolic disorders.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"1 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229962","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":"Clonal expansion of CD8+ effector T cells in patients with calcific aortic valve disease","authors":"Francesca Bartoli-Leonard, Sarvesh Chelvanambi, Tan Pham, Casandra L Clift, Mandy E Turner, Mark C Blaser, Sasha A Singh, Massimo Caputo, Masanori Aikawa, Amanda Pang, Jochen Muehlschlegel, Elena Aikawa","doi":"10.1093/cvr/cvag238","DOIUrl":"https://doi.org/10.1093/cvr/cvag238","url":null,"abstract":"Aims Calcific aortic valve disease (CAVD) is a complex cardiovascular pathology, culminating in aortic stenosis and heart failure with no effective treatment strategy, except invasive surgery. While inflammation may contribute to valvular fibro-calcific pathology and T cells have been identified within the leaflets, their contribution to CAVD pathogenesis remains unclear. Methods & Results Disease-staged whole-tissue proteomics (n=16) confirmed a pro-inflammatory T cell driven signature, with immunohistochemistry (n=10) and immunofluorescence (n=8) conducted on control and CAVD valves to confirm T cell localization to calcified regions. Flow cytometry immunophenotyping (n=20) was was performed using valvular tissue and corresponding peripheral blood from the same individuals. Single cell RNA sequencing and paired single T cell receptor sequencing was conducted on an additional 4 patients on CD45+, CD3+, CD4+ or CD8+ T cells. T cell signaling was identified through unsupervised clustering. Tissue resident memory (TRM) T cells were detected within the valve, exhibiting a highly cytotoxic, activated, and terminally differentiated phenotype. This pan-pro-inflammatory signal was differentially identified in T cells originating from the valve tissue, and not observed in the blood, indicative of an adaptive, local and non-systemic inflammatory signature in CAVD patients. T cell receptor analysis detected hyperexpanded clones within the CD8+ T cell central memory (TCM) population, with TRM cells comprising most of the large and medium clonal expansion within the T cell population. Clonal expansion was more prominent in valve tissue, with expanded clones largely confined to their tissue of origin. Clonal interaction network analysis demonstrated the greatest proportion of clones originating from CD8+ TCM and TRM populations, exhibiting a tissue resident, cytotoxic environment within the valve. Conclusions Taken together, the data define distinct T cell subpopulations in CAVD and implicate specific antigenic epitopes driving clonal expansion of valvular T cells, supporting a central role for antigen-driven, autoimmune-like inflammation in disease propagation.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"62 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229903","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":"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}