Cardiovascular Research最新文献

{"title":"Eicosapentaenoic acid (EPA) limits the more rapid oxidation of lipoprotein(a) [Lp(a)] compared with other ApoB particles","authors":"Samuel C R Sherratt, Peter Libby, Richard L Dunbar, Deepak L Bhatt, R Preston Mason","doi":"10.1093/cvr/cvaf144","DOIUrl":"https://doi.org/10.1093/cvr/cvaf144","url":null,"abstract":"Aims Elevated Lp(a) levels increase cardiovascular (CV) risk. Lp(a) contains oxidized phospholipids that may promote lipid oxidation more than other lipoproteins. The highly unsaturated omega˗3 fatty acid EPA has multiple double bonds that can trap free radicals in resonance structures. Purified ethyl-EPA reduced CV events in high-risk patients with elevated Lp(a) despite Lp(a)-associated risk elevation. Since Lp(a) is enriched in oxidized lipids, we hypothesized that Lp(a)-enriched plasma undergoes more rapid oxidation than other ApoB-containing particles, and that EPA limits oxidation of Lp(a)-enriched plasma more effectively than less-unsaturated fatty acids or other lipid lowering treatments. This property could limit the cellular stress responses in endothelial cells. Methods and Results Lp(a) was enriched to >50% total ApoB content to resemble an Lp(a)-associated “high risk” phenotype and compared with matching levels of small-dense LDL (sdLDL) and VLDL by isopycnic centrifugation. Samples were then incubated ± EPA (50 µM) at 37°C for 30 min. Oxidation was initiated with copper sulfate and monitored by malondialdehyde formation. We also subjected EPA to oxidation before measuring its antioxidant activity as compared with other long chain, less saturated fatty acids and lipid lowering agents. Human umbilical vein ECs (HUVECs) were incubated with Lp(a)-enriched plasma following oxidation in the absence and presence of EPA. Cell lysate samples were then analyzed by global LC/MS-based proteomics for significant changes in protein expression (>1-fold). Lp(a)-enriched plasma contained the highest baseline oxidized lipid (p<0.05) and underwent the most rapid oxidation. EPA, but neither the less unsaturated fatty acids nor lipid agents attenuated oxidation of each fraction through 4 hours (p<0.01). Oxidized EPA had diminished antioxidant capacity corresponding to the extent of oxidation. Attenuation of Lp(a) oxidation with EPA also mitigated pro-inflammatory and cellular stress response changes in protein expression. Conclusions Lp(a)-enriched plasma underwent more rapid oxidation than other ApoB-containing lipoproteins and promoted inflammatory changes in EC protein expression, a process attenuated by EPA. This action may contribute to reduced CV risk by EPA in those with elevated Lp(a) levels.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"15 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899208","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":"Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics","authors":"Patricia L Musolino, Susan J Rosser, Mairi Brittan, David E Newby, Colin Berry, Paul R Riley, Mauro Giacca, Roger J Hajjar, Andrew H Baker","doi":"10.1093/cvr/cvaf109","DOIUrl":"https://doi.org/10.1093/cvr/cvaf109","url":null,"abstract":"In the past decade, there has been substantive progress in gene therapy across disease indications. However, despite multiple gene therapies being approved for clinical use, none have a cardiovascular indication. Several reasons for this have inhibited or delayed progress in the cardiovascular field. First, developing cardiovascular gene therapeutics represents a substantial technical challenge, particularly relating to identifying and building effective delivery systems for therapeutic cargo that will be sufficient to gain meaningful efficacy with acceptable safety for the patient. Second, for genetic disease, gene editing therapy of pathogenic variants is at a relatively early stage of development. Third, since this is a field in development, the optimal design of clinical trials of cardiovascular gene therapies is also evolving and requires expert attention. Despite this, recent and current clinical trials are charting new ground, gaining valuable new patient-focused information that provides critical new learning and bench-to-bedside iterative development that has been so successful in other disease areas. While most clinical trials currently focus on cardiac gene therapy, vascular approaches are being developed, both genetic and common. We herein review the state-of-the-art in this rapidly progressing field of study. We consider gene therapy vector design, including transcriptional control, an area of incredible opportunity through engineering biology approaches to design, build, and test bespoke transcriptional units for expression of therapeutic cargo. Achieving progress in this exciting field will require close working between all stakeholders, including academic, clinical, industry, regulatory, and patient communities. Based on current progress, there is a 10-year horizon for bringing several cardiovascular gene therapies to licensing.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"3 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144899202","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":"Blood pressure management in secondary prevention after myocardial infarction","authors":"Massimo Volpe, Giovanna Gallo, Tomasz J Guzik, Bryan Williams, Franz H Messerli","doi":"10.1093/cvr/cvaf145","DOIUrl":"https://doi.org/10.1093/cvr/cvaf145","url":null,"abstract":"The management of blood pressure (BP) in secondary prevention after acute myocardial infarction (AMI) remains a matter of debate. Since no dedicated trials have specifically addressed BP control in patients recovering from an acute coronary syndrome, there are no evidence-based, prospective data to define precise BP targets in this population. Moreover, major international guidelines devote surprisingly little attention to BP management in the post-AMI setting, despite its recognized importance in reducing recurrent cardiovascular events. On one hand, BP-lowering may improve cardiac function by reducing afterload and myocardial oxygen consumption and by facilitating favorable ventricular remodeling. On the other, the concept of a J-shaped association—whereby excessive lowering of diastolic blood pressure (DBP) may paradoxically increase cardiovascular risk, particularly in the early post-acute myocardial infarction (AMI) period—remains a matter of ongoing uncertainty. Despite decades of investigation, this issue has not been definitively resolved and continues to raise debate within both the scientific community and among clinicians. In this review, we examine the current evidence supporting BP control in the context of secondary prevention following acute myocardial infarction (AMI), with an updated focus on the ongoing debate surrounding the potential implications of the J-shaped phenomenon.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"34 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906059","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 pioneer factor, ETV2, regulates networks to specify the embryonic endothelial lineage","authors":"Satyabrata Das, Xiao Ma, Kidus Hailemariam, Javier E Sierra-Pagan, Thijs A Larson, Young Geun Choi, Anh Quynh Le, Riley J Leonard, Austin Cho, Hesham A Sadek, Jianyi (Jay) Zhang, Mary G Garry, Xiao Dong, Wuming Gong, Daniel J Garry","doi":"10.1093/cvr/cvaf127","DOIUrl":"https://doi.org/10.1093/cvr/cvaf127","url":null,"abstract":"Aims Mechanisms that govern the emergence of multiple cell lineages from common mesodermal progenitors remain incompletely understood due to their limited number and accessibility. The pioneer transcription factor ETV2 sits at the top of the hematoendothelial (HE) lineage development molecular networks and directs both differentiation and reprogramming of endothelial lineage. In this study, we uncovered the transcriptional and epigenetic changes orchestrated by ETV2 to promote the HE lineage while suppressing other mesodermal lineages. Methods and results We isolated cells poised for skeletal muscle, cardiac and HE progenitor lineages by fluorescence activated cell sorting using the mouse embryonic stem cell-embryoid body (ES-EB) differentiation system over multiple time points with and without ETV2 overexpression. Analyzing these progenitor cells primed for distinct and different fate choices by single-cell RNA-sequencing and transposase-accessible chromatin sequencing (ATAC-seq), we defined the enhancers, transcriptional and epigenetic regulatory networks employed by ETV2 for its pioneer activity during HE lineage development. Overexpression of ETV2 directed the pluripotent cells towards a highly efficient generation of HE lineage at the expense of cardiac and skeletal muscle cell lineages. Dosage of ETV2 expression determined the sub-lineages of the HE progenitors. Tlr3 and Tlr4 were discovered as direct downstream targets of ETV2 contributing to the HE lineage development and their expression was dependent on ETV2 using overexpressing and null EBs. Master regulators of the cardiac lineage including Mesp1 were identified to be directly repressed by ETV2 in a context dependent fashion to suppress cardiac development in ETV2 overexpression cells. Repression of Mesp1 expression by ETV2 was further validated using Etv2 knock out (KO) EBs as well as stage-matched wild type (WT) and Etv2 null mouse embryos. Direct binding and down-regulation of Mesp1 by ETV2 overexpression was verified by chromatin immunoprecipitation sequencing, electrophoretic mobility shift assay (EMSA) and qPCR. Conclusion Collectively, our results define the functional role(s) played by ETV2 expression levels in the differential promotion and suppression of alternate fate choices of the mesodermal progenitor cells.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"18 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144901846","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":"GATA5/ISL1+ fibroblasts: the hidden architects of cardiac repair.","authors":"Sauri Hernandez-Resendiz, Elisa A Liehn, Derek J Hausenloy","doi":"10.1093/cvr/cvaf123","DOIUrl":"10.1093/cvr/cvaf123","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1311-1313"},"PeriodicalIF":13.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559308","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":"Rare pathogenic variants in G-protein-coupled receptor genes involved in gut-to-host communication are associated with cardiovascular disease risk.","authors":"Leticia Camargo Tavares, Rikeish R Muralitharan, Matthew Snelson, Francine Z Marques","doi":"10.1093/cvr/cvaf070","DOIUrl":"10.1093/cvr/cvaf070","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1316-1318"},"PeriodicalIF":13.3,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12352299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126886","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":"Assessing pulmonary artery stiffening with ultrasonography: a step forward for the assessment of pulmonary hypertension due to left heart disease?","authors":"Merve Keles, Allan Lawrie","doi":"10.1093/cvr/cvaf122","DOIUrl":"10.1093/cvr/cvaf122","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1314-1315"},"PeriodicalIF":13.3,"publicationDate":"2025-08-14","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 sex hormone decrease to hormonal treatment: impacts on cardiovascular risk with ageing.","authors":"Coralie Fontaine,Anna Gosset,Morgane Davezac,Mélissa Buscato,Virginie Grouthier,Marie-Ange Renault,Daniel Henrion,Florence Trémollières,Michael Schumacher,Françoise Lenfant,Jean-François Arnal","doi":"10.1093/cvr/cvaf086","DOIUrl":"https://doi.org/10.1093/cvr/cvaf086","url":null,"abstract":"Ageing plays a critical role in the deterioration of artery function and structure, and clearly represents the first cardiovascular (CV) risk factor in men but also in women. Coronary and cerebral arteries are particularly prone to atheroma, and the tissues they perfuse are particularly vulnerable to ischaemia. In both sexes, the age-related decrease in sex hormones (menopause and andropause) has deleterious effects on CV health. The extent to which hormonal supplementation can limit the CV risks increased by ageing remains controversial. The Women Health Initiative study, the main clinical intervention designed to evaluate the benefit/risk ratio of hormone treatment after menopause, revealed in 2002 an unexpected increase in CV events in aged women (>70 years) given estrogens plus a peculiar synthetic progestin medroxyprogesterone acetate, whereas estrogens alone were not harmful but even protective in younger women (<60 years). This pointed out the double problem of the progestin (now natural progesterone is preferred) and of the age. The clinical situation is not yet clear for testosterone and CV disease in men. Related to these questions, we will analyse and summarize: (i) the importance of the doses and concentrations of estrogens and testosterone, both in humans and in experimental models, allowing to define relevant/physiological or pharmacological actions of sex hormones in respect to their medical modulations in practice; (ii) the main clinical studies conducted with estrogens or androgens, in terms of CV protection and the impact of age on these effects; (iii) the mechanisms underlying these actions; (iv) the gender-affirming hormone therapy, as these sex hormones are the cornerstone of gender transition care management.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"134 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850911","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":"YY1 regulates vascular resistance and blood pressure dynamics through epigenetic control of m6A RNA modifications in VSMCs","authors":"Wenchu Ye, Wentao Gao, Cheng Kiu Ho, Lei Cui, James Y W Lau, Xiao Yu Tian, Bin Zhou, Kathy O Lui","doi":"10.1093/cvr/cvaf136","DOIUrl":"https://doi.org/10.1093/cvr/cvaf136","url":null,"abstract":"Aims Recent GWAS analysis has identified YY1 as a novel locus associated with blood pressure traits; however, whether YY1 directly controls vasoreactivity remains unknown. The principal function of vascular smooth muscle cells (VSMCs) is to contract, which is essential for regulating vascular tone, blood flow, and blood pressure. We hypothesized that YY1, a transcription factor, facilitates vascular function by epigenetically regulating gene expression in VSMCs. Methods and Results The effects of VSMC-specific YY1 loss were studied in mice. Lineage tracing, calcium imaging, and wire myography were performed to assess vasoreactivity. Genome-wide analysis through RNA-seq, ChIP-seq, m6A-seq, RNA immunoprecipitation, and transcript stability assays were conducted to evaluate gene expression and regulation. Co-immunoprecipitation was performed to study interactions between YY1 and chromatin regulators. AAV-mediated SM22-specific gene delivery was used to rescue vascular function in vivo. Contractile VSMCs were differentiated from human embryonic stem cells for in vitro experiments. Hypertension was induced in vivo using salt and L-NAME treatments. We demonstrate that vascular contraction and blood pressure are significantly reduced in Myh11CreER;Yy1fl/fl mice. YY1 does not regulate VSMC proliferation, survival, calcium entry, or membrane polarization in homeostasis. Integrative analyses of transcriptomics, epitranscriptomics, and epigenetics identified Mettl3 as a putative downstream target of YY1. Like YY1 loss-of-function, impaired vascular contraction and reduced blood pressure were observed in Myh11CreER;Mettl3fl/fl mice. Mylk2, Tgfb2, and Myh11 were significantly downregulated after genetic ablation of Yy1 or Mettl3 in VSMCs. Further analysis showed that Mettl3-mediated m6A mRNA methylation stabilizes the transcripts of these genes, possibly through the m6A reader IGF2BP1. AAV-mediated, VSMC-specific Mettl3 gene delivery significantly improved vascular contractility in Yy1-deficient mice, functionally confirming Mettl3 as a direct downstream target of YY1. Mechanistically, YY1 binds to the Mettl3 promoter near regions of H3K4 trimethylation and activates Mettl3 transcription by recruiting Set1A-Wdr82 complex for H3K3me3 deposition. Both Myh11CreER;Yy1fl/fl and Myh11CreER;Mettl3fl/fl mice exhibited delayed onset of hypertension. Conclusions YY1 maintains vascular contraction and regulates blood pressure by stabilizing Mylk2, Tgfb2, and Myh11 transcripts through the activation of Mettl3 transcription in VSMCs. These findings provide novel insights into the epigenetic control of VSMC epitranscriptomes and unravel a new mechanism underlying VSMC-mediated vasoconstriction through the YY1/Mettl3 regulatory axis. Additionally, our results demonstrate a clinically relevant role for the YY1/Mettl3 axis in mitigating hypertension and regulating blood pressure under both normal and hypertensive conditions.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"54 50 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825083","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":"A comprehensive review/expert statement on environmental risk factors of cardiovascular disease.","authors":"Thomas Münzel,Mette Sørensen,Jos Lelieveld,Philip J Landrigan,Marin Kuntic,Mark Nieuwenhuijsen,Mark R Miller,Alexandra Schneider,Andreas Daiber","doi":"10.1093/cvr/cvaf119","DOIUrl":"https://doi.org/10.1093/cvr/cvaf119","url":null,"abstract":"Cardiovascular disease (CVD) is the leading cause of mortality globally, with over 20 million deaths each year. While traditional risk factors-such as hypertension, diabetes, smoking, and poor diet-are well-established, emerging evidence underscores the profound impact of environmental exposures on cardiovascular health. Air pollution, particularly fine particulate matter (PM2.5), contributes to approximately 8.3 million deaths annually, with over half attributed to CVD. Similarly, noise pollution, heat extremes, toxic chemicals, and light pollution significantly increase the risk of CVD through mechanisms involving oxidative stress, inflammation, and circadian disruption. Recent translational and epidemiological studies show that chronic exposure to transport noise increases the risk of myocardial infarction, stroke, and heart failure. Air pollution, even below regulatory thresholds, promotes atherosclerosis, vascular dysfunction, and cardiac events. Novel threats such as micro- and nano-plastics are emerging as contributors to vascular injury and systemic inflammation. Climate change exacerbates these risks, with heatwaves and wildfires further compounding the cardiovascular burden, especially among vulnerable populations. The cumulative effects of these exposures-often interacting with behavioural and socioeconomic risk factors-are inadequately addressed in current prevention strategies. The exposome framework offers a comprehensive approach to integrating lifelong environmental exposures into cardiovascular risk assessment and prevention. Mitigation requires systemic interventions including stricter pollution standards, noise regulations, sustainable urban design, and green infrastructure. Addressing environmental determinants of CVD is essential for reducing the global disease burden. This review calls for urgent policy action and for integrating environmental health into clinical practice to safeguard cardiovascular health in the Anthropocene.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"6 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825085","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}