Cardiovascular Research最新文献

{"title":"Vascular nexus glia regulates vascular homeostasis and undergoes dynamic remodelling in deep vein thrombosis.","authors":"Kunhua Yang, Cheng Huang, Xuefeng Shi, Yumin Wu, Yi Lu, Yang Hu, Yuqiang Liu, Zhihui Qi, Ruizhe Tang, Jiaoyan Ren, Jie Xu, Fu-Li Xiang, Zhongxing Wang, Maojin Yao","doi":"10.1093/cvr/cvag180","DOIUrl":"https://doi.org/10.1093/cvr/cvag180","url":null,"abstract":"<p><strong>Aims: </strong>The cardiovascular system is tightly regulated by the nervous system, yet while cardiac nexus glial cells are known modulators of physiology, the identity and functional significance of glial populations within the vasculature remain poorly defined. We hypothesized that a specialized population of vascular glial cells exists in the adventitia and undergoes molecular and morphological remodelling under pathological stress.</p><p><strong>Methods and results: </strong>By analysing human and murine single-cell RNA sequencing (scRNA-seq) datasets, we identified a conserved population of glial cells in large vessels. Using hGFAP-Cre;tdTomato reporter mice and the Mosaic Analysis with Double Markers (MADM) system, we characterized these vascular nexus glia (VNGs) as an extensive reticular network in the adventitia that are in contact with sympathetic nerve fibres. To investigate functional necessity, we ablated the epigenetic regulator Suz12 in the GFAP lineage, which impaired VNG development and triggered vascular metabolic dysregulation. Cross-tissue transcriptomic integration revealed that VNGs possess a unique metabolic and stress-response signature compared to other glial subtypes. In a murine deep vein thrombosis model, time-resolved scRNA-seq and tissue clearing mapped a biphasic phenotypic transition. During thrombosis development, VNGs exhibit profound plasticity, undergoing morphological retraction and transitioning from a neuro-supportive state to an activated profile characterized by extracellular matrix reorganization and pro-fibrotic signalling.</p><p><strong>Conclusion: </strong>Our study identifies VNGs as a ubiquitous glial network within the vascular adventitia essential for homeostatic maintenance. By uncovering their Suz12-dependent development and dynamic remodelling during thrombotic injury, we provide a new conceptual framework for the neuro-vascular interface in venous thromboembolic disease.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905241","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":"DNMT3A-driven clonal haematopoiesis induces semaphorin 4A-dependent endothelial activation in heart failure.","authors":"Mariana Shumliakivska, Inga Hemmerling, Sebastian Cremer, Klara Kirschbaum, Marina Scheller, Xue Li, Carsten Müller-Tidow, Florian Leuschner, David John, Wesley Tyler Abplanalp, Andreas M Zeiher, Stefanie Dimmeler, Guillermo Luxán","doi":"10.1093/cvr/cvag192","DOIUrl":"https://doi.org/10.1093/cvr/cvag192","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890743","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":"Very-long chain fatty acids increase cell membrane thickness and impair mitochondrial function of aortic smooth muscle cells: implications for early vascular ageing.","authors":"Aleksandra Hliwa-Ślazyk, Magdalena Narajczyk, Magdalena Dzitkowska-Zabielska, Marika Franczak, Tomasz Sledzinski, Krzysztof Narkiewicz, Adriana Mika","doi":"10.1093/cvr/cvag191","DOIUrl":"https://doi.org/10.1093/cvr/cvag191","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879192","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":"Mechano-sensing channels PIEZO1 and PIEZO2 regulate mitral valve serotonin-mediated homeostasis and pathophysiology","authors":"Stanley J Stachelek, Emily J Hauber, Xiaoqiu Yang, Devin W Laurence, Vitali Rusinkevich, Peiran Lu, Estibaliz Castillero, Benjamin B Pressly, Claire Brady, Nikia T Toomey, Ilia Fishbein, Alexis Martinez, Alireza Mohammad Karim, Ephraim Jacobson, Dov Levine, Shawnaleh Cada, Kenneth B Margulies, Kenneth C Bedi, George M Anderson, Abba M Krieger, Liming Pei, Giovanni Ferrari, Robert J Levy","doi":"10.1093/cvr/cvag190","DOIUrl":"https://doi.org/10.1093/cvr/cvag190","url":null,"abstract":"Aims Mitral regurgitation (MR) pathophysiology involves increased serotonin (5-HT) receptor (HTR) expression and signaling, together with reduced 5-HT transporter (SLC6A4) expression in mitral valve interstitial cells (MVIC). The mechanosensitive calcium channels, PIEZO1 and PIEZO2, regulate cellular responses to a variety of mechanical conditions; however, PIEZO1 and PIEZO2 have not been studied in MR. We investigated the hypothesis that PIEZO1 and PIEZO2 mediate, through 5-HT mechanisms both homeostasis in normal mitral valves (nMV) and in the pathophysiology of MR. Methods and Results Immunofluorescence and Western blots demonstrated the presence of PIEZO1 and PIEZO2 in samples of explanted human nMV and MR. MVIC derived from nMV and MR leaflets also expressed PIEZO1 and PIEZO2. Single-cell RNA sequencing (scRNA-seq) analyses of nMV and MR leaflet samples from 9 MR and 5 nMV cases identified 7 different cell types: Endothelial cells, smooth muscle cells, T-cells, macrophages, and three distinct MVIC phenotypes, VIC1, VIC2, and VIC3. MVIC together comprised 97% of all valve cells, irrespective of valve pathology. In addition, scRNA-seq of nMV and MR leaflets demonstrated MVIC PIEZO1 and PIEZO2 expression, together with HTR2B and SLC6A4. MVIC cultures, with no added 5-HT, demonstrated that PIEZO1 activation with its agonist, Yoda1, increased MVIC Ca2+ uptake. This was inhibited by PIEZO1-siRNA, and Dooku1, a Yoda1 antagonist, but not PIEZO2-siRNA or noncoding-RNA. Additional MVIC studies revealed that in static MVIC cultures, PIEZO1 activation with Yoda1 downregulated SLC6A4, upregulated HTR2B, and increased 5-HT levels and protein synthesis. Cyclic tension MVIC bioreactor studies showed that either PIEZO1-siRNA or PIEZO2-siRNA mitigated tension induced SLC6A4 downregulation and increased collagen synthesis; only PIEZO2-siRNA mitigated both static and cyclic tension-induced MVIC 5-HT production. Conclusions Our findings have identified a novel link between mechano-transduction, 5-HT production and receptor signaling, and collagen synthesis, suggesting PIEZO1, PIEZO2, and downstream 5-HT pathways as potential therapeutic targets for mitigating MR progression.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"43 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877308","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-specific associations of the plasma-proteome with incident coronary artery disease","authors":"Vincent Q Sier, Kristina Dimitrova, Erna H A B Peters, Wouter P M van der Loo, Ko Willems van Dijk, Diana van Heemst, Wilhelmina H Bax, Paul H A Quax, Gerard Pasterkamp, Michal Mokry, J Wouter Jukema, Raymond Noordam, Margreet R de Vries","doi":"10.1093/cvr/cvag186","DOIUrl":"https://doi.org/10.1093/cvr/cvag186","url":null,"abstract":"Aims The etiology of coronary artery Disease (CAD) appears different for men and women, yet insights into underlying sex-specific biological mechanisms are limited. We integrated genomic and proteomic analyses to investigate sex-specific associations of the plasma-proteome with CAD. Methods and Results In 40,829 UK Biobank participants (free-of-CAD, baseline-365 days thereafter; 55% women; mean age 56.9 ± 8.1 years), we examined associations between 2,922 plasma proteins and incident CAD over a median follow-up of 13.7 years (IQR 13.1-14.4) using multivariable-adjusted Cox proportional hazards models. Sex-specific analyses identified 440 female exclusive and 32 male exclusive proteins associated with incident CAD (FDR-corrected p &amp;lt; 0.05), revealing distinct pathway enrichments, including innate immune response in women and angiogenesis in men. Causality was assessed through combined and sex-stratified two-sample Mendelian randomization (MR) using inverse-variance-weighted analyses with genome wide association summary statistics from 422,108 men (61,969 cases) and 521,695 women (27,128 cases) (UK Biobank, FinnGen freeze 9). Integration of direct sex-protein interaction analyses with sex-combined MR identified 59 proteins with evidence for sex-specific causal effects. Four proteins demonstrated concordant directionality in sex-stratified MR analyses (n = 943,803) and multivariable regression models, namely CDKN2D, MYH9, and SKAP2 (women), and CTSH (men). To assess translational relevance, prioritized targets were further evaluated in secondary major adverse cardiovascular events among carotid endarterectomy patients (MACE; Athero-Express) and acute myocardial infarction (AMI; MISSION!) using plasma proteomics and ELISA. After further top-target identification in the context of MACE and AMI, clinical drug candidates were identified through a machine learning framework, including CTSH (men), and TNFRSF4 (both sexes). Conclusions We identified sex-specific associations of proteins and biological pathways with incident CAD. Whereas the majority of proteins had consistent associations in both men and women, our findings suggest a degree of sex-specific pathogenesis with evidence for potential causality, opening new alleys for tailored prevention strategies and clinical cardiovascular risk management.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"184 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148877309","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":"Early encounters with hypertrophic cardiomyopathy.","authors":"Eugene Braunwald","doi":"10.1093/cvr/cvag094","DOIUrl":"https://doi.org/10.1093/cvr/cvag094","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872806","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":"Incremental prognostic value of late gadolinium enhancement in hypertrophic cardiomyopathy in a large contemporary cohort.","authors":"Susan K Keen, Stuti Shah, Hesham Sheashaa, Mohammed Abusafia, Shada Jadam, Simrat Kaur, Andrew Gaballa, Susan Ospina, Katy Rutkowski, Jay Ramchand, Zoran B Popovic, Maran Thamilarasan, Nicholas G Smedira, Paul Schoenhagen, Bo Xu, Michael Bolen, Milind Y Desai","doi":"10.1093/cvr/cvag181","DOIUrl":"https://doi.org/10.1093/cvr/cvag181","url":null,"abstract":"<p><p>This large contemporary cohort included 3,035 patients (median age 58 years, 57% men); 56% had LGE, including 242 (8%) with LGE > 10%. Most patients have obstructive HCM (71%), 1498 (69%) of which subsequently underwent septal reduction therapy (SRT) at a median of 43 days (interquartile range [IQR] 5-107) from the CMR date (1,485 myectomies and 13 alcohol septal ablations). Over a median of 8.8 years, 331 (11%) primary endpoints occurred (295 cardiovascular deaths [9.7%] and 36 appropriate ICD discharges [1.3%]). On multivariable Cox proportional hazards analysis (adjusted for standard clinical and CMR variables, higher %LGE (1.05 per 1% increase, 95% CI 1.03-1.06; p < 0.001) was associated with primary events. Compared with no LGE, LGE ≥10% was associated with higher risk of the composite endpoint.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863299","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":"Thyroid-stimulating hormone enhances platelet activation and arterial thrombosis.","authors":"Peng Zhang, Luning Zhou, Huajie Xu, Haoxuan Zhong, Wenxuan Zhou, Xin Zhao, Xiaotong Liu, Xiaoming Zhu, Hongyi Wu, Zhiyong Qi, Junbo Ge","doi":"10.1093/cvr/cvag187","DOIUrl":"https://doi.org/10.1093/cvr/cvag187","url":null,"abstract":"<p><strong>Aims: </strong>Thyroid-stimulating hormone (TSH), elevated in conditions like subclinical hypothyroidism, has been clinically linked to a higher risk of morbidity and mortality in patients with coronary artery disease (CAD). Here, we aim to investigate the effects of TSH on CAD-associated platelet activation and arterial thrombosis, along with the underlying mechanisms.</p><p><strong>Methods and results: </strong>Clinical study demonstrated that higher TSH levels are associated with an increased risk of major adverse cardiovascular events in CAD patients. In vitro human and mouse platelet function studies found that TSH potentiates agonist-induced platelet aggregation, dense granule adenosine triphosphate release, integrin alpha-IIb beta-3 activation, P-selectin release from α-granules, platelet spreading, and clot retraction. Furthermore, in vivo animal studies demonstrated that TSH enhances thrombosis, whole blood thrombus formation, and middle cerebral artery occlusion-induced brain injury. Mechanistic studies revealed that platelets express the TSH receptor (TSHR). TSH binds to platelet TSHR and activates both the Gs/cAMP/PKA and Gq/Ca2+/PKC/MAPK signaling pathways. Activation of the Gq pathway is more pronounced than that of the Gs pathway, thereby potentiating platelet activation. Finally, our in vivo work showed that TSH aggravates microvascular obstruction and promotes myocardial infarction expansion in a mouse myocardial ischeamia/reperfusion injury model.</p><p><strong>Conclusion: </strong>TSH augments platelet activation and in vivo thrombus formation through engagement of platelet TSHR, subsequently activating downstream signaling cascades involving Gs/cAMP/PKA and Gq/Ca2+/PKC/MAPK pathways.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839215","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 gut-heart axis in cardio-oncology.","authors":"Nicole S L Chan, Courtney Cross, Joanne Bowen, Clive Prestidge, Feargal J Ryan, Mohsen Dorraki, Sanuri Liyanage, Shiwani Sharma, Rajesh Pathy, Christina A Bursill, Peter J Psaltis, Francine Z Marques, Hannah R Wardill, Paul Joyce","doi":"10.1093/cvr/cvag146","DOIUrl":"10.1093/cvr/cvag146","url":null,"abstract":"<p><p>As cancer survival rates improve, the long-term burden of treatment has become increasingly evident. Cancer survivors face a markedly higher risk of cardiovascular-related complications and premature, non-cancer-related mortality. In particular, cardiovascular disease (CVD) is disproportionately prevalent, with survivors approximately 40% more likely to develop and die from CVD compared to the general population. Although this increased morbidity reflects both acute cardiotoxic events and the later development and progression of more chronic CVDs, traditionally viewed as direct consequences of cancer therapies, the underlying mechanisms, especially those that are feasible to modify, are poorly understood. Emerging evidence positions the gut-heart axis as a central regulator of cardiovascular risk in cardio-oncology. This avenue is especially compelling to explore as the gut microbiome is well documented to be altered by cancer therapies, including chemotherapy, immune checkpoint inhibitors, targeted therapies, and radiation, with profound and persistent changes in diversity, composition and function widely reported across clinical cohorts. Comparable microbial changes have been observed in non-cancer cohorts with cardiovascular disease. For example, specific microbial metabolites have been reported to exert cardiovascular protective benefits in hypertension. Thus, there is a compelling opportunity to explore the gut microbiome to advance our understanding and ability to prevent cardiovascular disease in cancer survivors. This review synthesizes current evidence linking the gut microbiome to cancer therapy-related cardiac dysfunction (CTRCD), evaluates microbial metabolites as predictive biomarkers of cardiotoxicity, and discusses microbiome-targeted modulation as an emerging strategy for improving cardiovascular outcomes in cancer survivors.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1573-1588"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350880","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":"KMT2B drives inflammation in endothelial cells and promotes atherosclerosis via histone H3 lysine 4 trimethylation-mediated autophagy.","authors":"Fuyuan Zhang, Rong Fu, Zhongxiao Lin, Qingwen Hu, Dechong Zheng, Hao Zhang, Yu Huang, Menglin Zhu, Liuyi Lu, Wen Shu, Yibo Li, Juntao Kan, Qian Ding, Yi Zhun Zhu","doi":"10.1093/cvr/cvag142","DOIUrl":"10.1093/cvr/cvag142","url":null,"abstract":"<p><strong>Aims: </strong>Atherosclerosis is a chronic condition characterized by persistent inflammation and vascular remodeling. Oxidized low-density lipoprotein (ox-LDL) plays a central role in this process by promoting inflammation and inducing epigenetic modifications. This study aimed to investigate the role of KMT2B, a histone methyltransferase, in regulating inflammation and autophagy in endothelial cells (ECs) during atherosclerosis.</p><p><strong>Methods and results: </strong>ApoE-/- mice were fed a western diet for 2, 4, 8, and 12 weeks to assess epigenetic modifications during atherosclerosis. In vitro, rat aortic endothelial cells (RAECs) and human aortic endothelial cells (HAECs) were exposed to ox-LDL at various time points. To study the role of KMT2B in inflammation, small-interfering RNA-mediated knockdown and plasmid overexpression were employed to manipulate KMT2B expression in RAECs and HAECs. In vivo, Kmt2b was knocked down using lentivirus-expressed sgKmt2b in ApoE-/- mice, and its impact on atherosclerotic plaque formation, lipid accumulation, and inflammatory cytokines was evaluated. To explore the mechanism by which ox-LDL regulates the expression of KMT2B, reactive oxygen species (ROS) levels were detected, and siSyk and siFos were performed in RAECs. Western diet feeding of ApoE-/- mice resulted in elevated KMT2B expression and H3K4me3 levels in atherosclerotic plaques, particularly in ECs and macrophages. KMT2B was found to directly regulate autophagy, followed by the regulation of inflammation. Furthermore, inhibiting the expression of KMT2B in ApoE-/- mice improved atherosclerosis and suppressed inflammation. The transcription factor Fos mediated KMT2B expression through Syk- and ROS-dependent signaling, enhancing its binding to the Kmt2b promoter region.</p><p><strong>Conclusion: </strong>KMT2B is a critical regulator of autophagy and inflammation in atherosclerosis, with Fos-mediated signaling driving its expression. Targeting KMT2B may offer a promising therapeutic strategy for modulating inflammation and plaque progression in atherosclerosis.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1609-1625"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547965","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}