Cardiovascular Research最新文献

{"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}

{"title":"Hypoxia suppresses platelet activity through GPVI down-regulation but paradoxically enhances arterial thrombosis via elevated vWF.","authors":"Vishwanath Jha, Jae-Sung Kim, Muteen Ahmed, Joseph E Italiano, Babak Razani, Jaehyung Cho","doi":"10.1093/cvr/cvag123","DOIUrl":"10.1093/cvr/cvag123","url":null,"abstract":"<p><strong>Aims: </strong>Hypoxia is associated with thrombosis, yet its effects on platelet function remain controversial due to variable experimental conditions. In this study, we systematically examined the effects of graded normobaric hypoxia on platelet function and arterial thrombosis in mice.</p><p><strong>Methods and results: </strong>Exposure to 8% O2 for 6 days increased red blood cell counts, haemoglobin, and haematocrit, recapitulating human hypoxic adaptation. Platelets from hypoxic mice show reduced activation and aggregation in response to multiple agonists, including thrombin and collagen-related peptide, with defects accentuated by more severe (8% vs. 12% O2) or prolonged (6-day vs. 4-day) hypoxia and most pronounced after glycoprotein VI (GPVI) stimulation. Similar platelet dysfunction occurs in humans after 4-day hypoxia (∼12% O2) followed by 4-day normoxia. Quantitative mass spectrometry identifies down-regulation of lysozyme, Hsp90 signalling molecules, and GPVI. Pathway and systems-level network analyses reveal significant down-regulation of Hsp90-involved protein folding and GPVI-mediated signalling pathways. Deletion of platelet lysozyme or Hsp90β, however, minimally affects platelet function, indicating regulation by multiple signalling pathways under hypoxia. We confirmed that GPVI levels are significantly reduced in platelets, while ADAM10 levels remain unchanged, suggesting hypoxia-induced GPVI down-regulation. Hypoxic blood forms smaller thrombi on collagen under arterial shear. Paradoxically, hypoxic mice exhibit enhanced arterial thrombosis and shortened tail bleeding times. Biochemical and mass spectrometry analyses of mouse plasma demonstrate elevated circulating von Willebrand factor under hypoxia.</p><p><strong>Conclusion: </strong>These results uncover a paradox under hypoxia: despite GPVI down-regulation and impaired agonist-induced platelet activation, elevated plasma von Willebrand factor drives enhanced arterial thrombosis. This multilayered regulation provides mechanistic insight into hypoxia-associated thrombotic risk and may inform therapeutic strategies.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1688-1704"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155062","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":"Retraction of: Heat shock factor-1 knockout enhances cholesterol 7α-hydroxylase (CYP7A1) and multidrug transporter (MDR1) gene expressions to attenuate atherosclerosis.","authors":"","doi":"10.1093/cvr/cvag128","DOIUrl":"10.1093/cvr/cvag128","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1724"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307300","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":"Deletion of endothelial SOX9 reverses ageing-induced cardiac dysfunction.","authors":"Felix A Trogisch, Manuela Fuhrmann, Aya Abouissa, Julio Cordero, Dilraj Kaur, Stefanie Uhlig, Anne Birke, Karla Vollmerig, Kalim Allah Najib, Javier Llansol Muñoz, Nina Weinzierl, Ellen Hofmann, Carolina de la Torre, Volker Ast, Christian Schulz, Gergana Dobreva, Joerg Heineke","doi":"10.1093/cvr/cvag120","DOIUrl":"10.1093/cvr/cvag120","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1550-1554"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148052825","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":"Ultrafine particles: rethinking air pollution risk.","authors":"Marek Rajzer, Wiktoria Wojciechowska","doi":"10.1093/cvr/cvag161","DOIUrl":"10.1093/cvr/cvag161","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1546-1547"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148547987","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 DECAF trial: coffee, caffeine, and atrial fibrillation.","authors":"Christopher X Wong, Gregory M Marcus","doi":"10.1093/cvr/cvag155","DOIUrl":"10.1093/cvr/cvag155","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1543-1545"},"PeriodicalIF":12.5,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148673141","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":"JCAD/KIAA1462: biology, pathophysiology, and translational perspectives in vascular disease.","authors":"Margherita Moriero, Simon Kraler, Amedeo Tirandi, Davide Di Vece, Thomas F Luscher, Federico Carbone, Davide Ramoni, Aldo Bonaventura, Giovanni G Camici, Fabrizio Montecucco, Stefano Ministrini, Yifan Wang, Luca Liberale","doi":"10.1093/cvr/cvag182","DOIUrl":"https://doi.org/10.1093/cvr/cvag182","url":null,"abstract":"<p><p>Junctional cadherin 5-associated protein (JCAD/KIAA1462) is an endothelial junctional protein encoded by a locus robustly associated with coronary artery disease and myocardial infarction in genome-wide association studies. Initially identified as a structural component of endothelial cell-cell junctions, JCAD has since emerged as a mechanosensor and regulator of key intracellular pathways (i.e. Hippo/YAP, PI3 K/Akt, and MAPK/ERK) with functional consequences for endothelial homeostasis, inflammation, and vascular tone. In this review, we summarise the current understanding of JCAD biology, from its molecular features and pathway interactions to its experimental roles in atherosclerosis, arterial thrombosis, and ischaemic stroke. We further discuss emerging translational evidence suggesting circulating JCAD as an independent predictor of adverse cardiovascular events in patients with acute coronary syndromes, and its prognostic potential in ischaemic stroke. The review also addresses the expanding biology of JCAD within the cardiovascular system, hypothesizing links to conditions such as hypertension, heart failure with preserved ejection fraction, and calcific aortic valve disease, as well as key limitations and therapeutic challenges. Overall, the available evidence highlights JCAD as a biologically plausible and potentially clinically relevant endothelial mediator, though independent validation and substantial mechanistic work remain necessary before its translational potential can be fully realized.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817593","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}