Cardiovascular Research最新文献

{"title":"Platelets and inflammation - insights from platelet non-coding RNA content and release in the Bruneck Study and the PACMAN-AMI trial","authors":"Clemens Gutmann, Temo Barwari, Christian Schulte, Konstantinos Theofilatos, Bhawana Singh, Kaloyan Takov, Gonca Suna, Melissa V Chan, Paul C Armstrong, Christian Cassel, Yasushi Ueki, Jonas D Häner, Peter Santer, Peter Willeit, Christian Hengstenberg, Lorenz Räber, Stefan Kiechl, Johann Willeit, Timothy D Warner, Manuel Mayr","doi":"10.1093/cvr/cvaf100","DOIUrl":"https://doi.org/10.1093/cvr/cvaf100","url":null,"abstract":"Aims Platelets contain non-coding RNAs (ncRNAs), and their measurement may complement platelet aggregometry. Methods and results In the community-based Bruneck Study (n = 338), we generated platelet-rich plasma (PRP), platelet-poor plasma (PPP) and platelets. PRP was subjected to aggregometry using various agonists and processed to platelet releasates thereafter. Releasates, PPP and platelets underwent real-time polymerase chain reactions to measure ncRNAs. Platelet ncRNA release appeared agonist-specific, dose-dependent, and inhibited by aspirin. Collagen triggered the strongest release for most ncRNAs, whereas miR-150 was hyperresponsive to ADP, and miR-21 was hyperresponsive to arachidonic acid. Comparing the dynamic range of ncRNA release to aggregation, aggregation reached a maximum at high agonist concentrations, while ncRNAs continued to rise. Cohort-wide associations showed that inflammation parameters like neutrophil counts and C-reactive protein correlated inversely with platelet aggregation and ncRNA release. Similarly, a high leukocyte-derived RNA content in isolated platelets correlated inversely with aggregation. Inverse correlations were absent in aspirin users. Through experiments on plasma-free platelet releasates and platelets, including size-exclusion chromatography, ultracentrifugation and degradation assays, we discovered that microRNAs and YRNAs are carried by proteins and readily released, while circular-, long non-coding- and messenger RNAs are carried by vesicles and preferentially retained. Finally, we assessed ncRNA responses to short- and long-term dual antiplatelet therapy (DAPT) in plasma from 265 patients with acute myocardial infarction (AMI) of the PACMAN-AMI trial. Most of the DAPT effect was already achieved by 4 weeks, with a further reduction at 52 weeks, revealing a short- and long-term DAPT effect not captured by aggregometry. Conclusions Inflammation and leukocyte-derived RNAs in isolated platelets are associated with reduced platelet responses ex vivo, potentially reflecting exhaustion through pre-activation in vivo. We show that protein-bound ncRNAs are readily released from platelets, whereas vesicle-bound ncRNAs are preferentially retained. We highlight the potential of ncRNAs as biomarkers complementing aggregometry.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"15 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210823","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":"Adverse cardiac events associated with antibody drug conjugates in cancer patients: a retrospective analysis on the FAERS database and randomized controlled trials","authors":"Shaowei Zhuang, Bitao Wang, Enmin Wu, Jierong Lin, Wanxian Zeng, Maobai Liu, Jing Yang, Xiujuan Zhang","doi":"10.1093/cvr/cvaf095","DOIUrl":"https://doi.org/10.1093/cvr/cvaf095","url":null,"abstract":"Aims Antibody Drug Conjugates(ADCs) are approved for use in cancers. Cardiovascular adverse reaction is a fatal adverse reactions associated with ADCs. The incidence of adverse cardiac events about ADCs have not been fully studied. We aimed to assess differences in cardiotoxicity among cancer patients treated with different ADCs. Methods and Results An observational retrospective pharmacovigilance study of ADC-related adverse cardiac events was conducted based on the FDA Adverse Event Reporting System (FAERS) and Open tools for data mining and analysis of pharmacoVigilance data (OpenVigil 2.1) website. We conducted a comprehensive search of articles published before January 24, 2024, using PubMed, Web of Science, Cochrane Library, Scopus, CINAHL, Embase databases, and the Clinical Trials website(https://clinicaltrials.gov). Primary outcomes include any cardiotoxicity. Secondary outcomes focused on heart failure. Network meta-analysis and subgroup analyses were conducted to synthesize results based on relative risk(RR) values. SUCRA values were calculated for risk ranking among ADCs according to the types and target of ADCs. 1522 cases of cardiac adverse events from FAERS associated with ADC treatments. All ADCs showed disproportionate association in cardiac adverse events. Gender and age factors are considered to have an influential role in the cardiotoxicity induced by Antibody-Drug Conjugates (ADCs). The network meta-analysis showed that the overall incidence rate was 17.12% (95% CI: 13.36%, 20.88%). Brentuximab vedotin has the RR value of 1.78(95%CI:1.13,2.82). HER-2 targeted ADCs has the RR value of 0.61(95%CI:0.42,0.89).Polatuzumab vedotin and enfortumab vedotin have SUCRA values of 82.6 and 22.0, respectively. The SUCRA values of ADC targeting FRα and TROP-2 were 75.6 and 18.8, respectively. Conclusion Cardiac adverse events are associated with ADCs. ADCs targeting HER-2 show lower cardiac toxicity. Brentuximab vedotin is associated with higher cardiac toxicity. Polatuzumab vedotin has the highest risk for cardiac toxicity and Enfortumab vedotin has the lowest risk. ADC targeting FRα has the highest risk of cardiotoxicity and ADC targeting TROP-2 has the lowest risk.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"11 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201925","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":"Targeting CD8+ T cells in cardiovascular diseases - current options and therapeutic perspectives","authors":"Rida Al-Rifai, Vincent Duval, Icia Santos-Zas, Théo Guyon, Luna Chetrit, Corinne Tanchot, Clement Cochain, Alma Zernecke, Marc Vocanson, Benoit Bensaid, Alain Tedgui, Heinz-Peter Schultheiss, Christian Baumeier, Christian Bailly, Hafid Ait-Oufella","doi":"10.1093/cvr/cvaf098","DOIUrl":"https://doi.org/10.1093/cvr/cvaf098","url":null,"abstract":"T lymphocytes expressing the CD8 coreceptor, often referred to as cytotoxic T-lymphocytes (CTL), are critical in defending against virus infections and cancers. CD8 encompasses a diverse family of proteins, including homodimers, heterodimers, isoforms, and splice variants. CD8αβ heterodimers are the predominant form of the CD8 membrane protein, often anchored to lipid rafts to facilitate the activation of the T cell receptor (TCR). Small molecules like itaconate have been shown to modulate CD8+ T cell expression. Anti-CD8 monoclonal antibodies (mAbs) targeting either CD8α or CD8β are available to study the functions of CD8+ cells in experimental models. Additionally, various immuno-imaging probes, such as 89Zr-crefmirlimab berdoxam, have been developed to predict the response of cancers to immunotherapy. The potential use of anti-CD8 mAbs to treat diseases associated with hyperactivation of cytotoxic CD8+ T cells is also under investigation. This includes conditions such as acute (e.g., ischemic heart failure, ischemic stroke), subacute (e.g., myocarditis) and chronic cardiovascular diseases (atherosclerosis). The use of anti-CD8 mAbs represents a promising therapeutic strategy to combat diseases characterized by excessive cytolytic activity of T cells. Experimental models have shown that anti-CD8 depleting mAbs can effectively limit tissue damages caused by CD8+ T cells. As a result, the time is ripe to evaluate these treatments in humans. Preclinical development of the first therapeutic anti-CD8 mAb (PLG101) is currently underway.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"28 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189003","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":"Sweeteners: erythritol, xylitol and cardiovascular risk - friend or foe?","authors":"Bettina K Wölnerhanssen, Anne Christin Meyer-Gerspach, Arduino Arduini, Angelo D’Alessandro, Edoardo Gronda, Stefano Carugo, Mario Bonomini, Maurizio Gallieni, Valentina Masola, Anne Angelillo-Scherrer, Tommaso Prosdocimi, Gary D Lopaschuk","doi":"10.1093/cvr/cvaf091","DOIUrl":"https://doi.org/10.1093/cvr/cvaf091","url":null,"abstract":"Hyperglycemia harms vascular health and promotes platelet aggregation. Reducing glucose concentration is crucial, and sugar alcohols may aid this effort. Used for over 50 years in food, cosmetic, and pharmaceutical industries, erythritol and xylitol minimally affect plasma glucose and insulin levels while promoting the release of beneficial gastrointestinal hormones such as e.g. glucagon-like peptide-1 (GLP-1). These properties make them particularly appealing for individuals with diabetes, obesity, and metabolic syndrome. Recent pilot trials suggest that xylitol and erythritol might temporarily alter platelet aggregation. Studies on critically ill patients receiving large intravenous doses and Mendelian randomization trials do not link sugar alcohols to significant cardiovascular risks. Sugar alcohols are also endogenously produced in the body, and while their increased production under certain conditions is not fully understood, it requires further research. This review discusses the physiology and metabolism of erythritol and xylitol, and other sugar alcohols, their roles in metabolomic profiling, effects on platelet aggregation and cardiovascular risk, related genetic disorders, vascular impacts, and usage in critically ill patients.","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":"35 1","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176618","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":"PRDM16, a new kid on the block in cardiovascular health and disease.","authors":"Jore Van Wauwe, Hannelore Kemps, Pieter Vrancaert, Alexia Mahy, Robin Schellingen, Mandy O J Grootaert, Manu Beerens, Aernout Luttun","doi":"10.1093/cvr/cvaf089","DOIUrl":"https://doi.org/10.1093/cvr/cvaf089","url":null,"abstract":"<p><p>Transcriptional regulation is essential for the development, homeostasis, and function of all organisms. Transcription factors and epigenetic modifiers play an indispensable role by direct or indirect interaction with DNA or chromatin. Although the role of transcription factor PRDM16 in adipose, hematopoietic, skeletal, and neural cell lineage specification is well-documented, its function within the cardiovascular system has only recently gained significant attention. Similar as in adipose tissue, PRDM16 displays an asymmetric expression pattern within the cardiovascular system, where it is exclusively expressed by ventricular cardiomyocytes and endothelial and smooth muscle cells of arteries, while being absent in their atrial and venous counterparts. Concordantly, an increasing number of clinical and preclinical studies have identified PRDM16 as an important multi-modal regulator of cardiovascular development and function. Moreover, aberrant PRDM16 expression has now been linked to (cardio)vascular diseases, including left ventricular non-compaction, migraine, and coronary artery disease. In this review, we give a synopsis of PRDM16's expression and function within (developing) cardiovascular tissues and provide insights into how impaired PRDM16 signaling contributes to cardiovascular disease.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172729","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":"Targeted delivery of TAPI-1 via biomimetic nanoparticles ameliorates post-infarct left ventricle function and remodelling.","authors":"Qing Chen, Yang Yu, Lei Tong, Robert M Weiss, Shun-Guang Wei","doi":"10.1093/cvr/cvaf039","DOIUrl":"10.1093/cvr/cvaf039","url":null,"abstract":"<p><strong>Aims: </strong>The potential of nanoparticles as effective drug delivery tools for treating failing hearts in heart failure remains a challenge. Leveraging the rapid infiltration of neutrophils into infarcted hearts after myocardial infarction (MI), we developed a nanoparticle platform engineered with neutrophil membrane proteins for the targeted delivery of TAPI-1, a TACE/ADAM17 inhibitor, to the inflamed myocardium, aiming to treat cardiac dysfunction and remodelling in rats with MI.</p><p><strong>Methods and results: </strong>Neutrophil-mimic liposomal nanoparticles (Neu-LNPs) were constructed by integrating synthesized liposomal nanoparticles with LPS-stimulated neutrophil membrane fragments and then loaded with TAPI-1. MI rats were treated with TAPI-1 delivered via Neu-LNPs for 4 weeks. Left ventricular function was assessed by echocardiography and cardiac fibrosis was evaluated post-treatment. The novel Neu-LNPs maintained typical nanoparticle features, but with increased biocompatibility. Neu-LNPs demonstrated improved targeting ability and cellular internalization, facilitated by LFA1/Mac1/ICAM-1 interaction. Neu-LNPs displayed higher accumulation and cellular uptake by macrophages and cardiomyocytes in infarcted hearts post-MI, with a sustained duration. Treatments with TAPI-1-Neu-LNPs demonstrated greater protection against myocardial injury and cardiac dysfunction in MI rats compared to untargeted TAPI-1, along with reduced cardiac collagen deposition and expression of fibrosis biomarkers as well as altered immune cell compositions within the hearts.</p><p><strong>Conclusions: </strong>Targeted treatment with TACE/ADAM17 inhibitor delivered via biomimetic nanoparticles exhibited pronounced advantages in improving left ventricle function, mitigating cardiac remodelling, and reducing inflammatory responses within the infarcted hearts. This study underscores the effectiveness of Neu-LNPs as a drug delivery strategy to enhance therapeutic efficacy in clinical settings.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"760-774"},"PeriodicalIF":10.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555990","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":"Pre-ischaemic empagliflozin treatment attenuates blood-brain barrier disruption via β-catenin mediated protection of cerebral endothelial cells.","authors":"Guohao Liu, Yanmei Qiu, Nanlin You, Mengchen Yu, Wenbo Chen, Tao Sun, Zhen Qin, Mengtao Han, Zhiwei Xue, Xiangjun Liang, Bo Mao, Lu Ling, Yanzhao Wu, Wenchen Xing, Quanmeng Liu, Donghai Wang","doi":"10.1093/cvr/cvaf026","DOIUrl":"10.1093/cvr/cvaf026","url":null,"abstract":"<p><strong>Aims: </strong>Microvascular endothelial cells dysfunction can significantly worsen ischaemic stroke outcomes by disrupting tight junctions and increasing the acquisition of adhesion molecules, accelerating blood-brain barrier (BBB) disruption and pro-inflammatory response. The identification of drugs that improve endothelial cell function may be crucial for ischaemic stroke. It has been validated that empagliflozin (EMPA), a novel antidiabetic drug, protects endothelial cells regardless of the diabetic status of the patient. However, the impact of EMPA on stroke outcomes is unclear. We hypothesized that EMPA would exert a beneficial effect on ischaemic stroke outcome by protecting microvascular endothelial cells against tight junction disruption and the increase of adhesion molecules.</p><p><strong>Methods and results: </strong>Young adult male mice were administered with EMPA or vehicle (dimethyl sulfoxide) daily for 7 days before being subjected to transient middle cerebral artery occlusion (tMCAO). Neurological deficits were evaluated for up to 28 days post-tMCAO. Infarct volume, BBB disruption, and inflammatory status were assessed 1 day after tMCAO.bEnd.3 cells and primary brain microvascular endothelial cells were treated with EMPA or vehicle under oxygen and glucose deprivation/reperfusion (OGD/R), and the lactate dehydrogenase release, transendothelial electrical resistance, leakage of fluorescein isothiocyanate-dextran, and tight junction and adhesion molecules proteins were examined. Mechanistic studies probing the effect of EMPA on endothelial cells were conducted by RNA-seq. EMPA treatment before ischaemia markedly improved infarct volume, BBB disruption, and inflammation 1-day post-tMCAO, and further enhanced neurobehavioral function up to 28 days. Pre-treatment of EMPA attenuated endothelial cell dysfunction under OGD/R conditions. In mechanistic terms, RNA-seq data from isolated cerebral microvessels revealed that the Wnt/β-catenin signalling pathway was preserved in the EMPA group, in contrast to the vehicle group. Pre-treatment with EMPA inhibited β-catenin ubiquitination and promoted β-catenin translocation from the cytoplasm to the nucleus to improve endothelial cell function. Importantly, the β-catenin inhibitor XAV-939 eliminated this protective function of EMPA.</p><p><strong>Conclusion: </strong>EMPA administration before tMCAO attenuated ischaemia/reperfusion-induced BBB disruption and inflammation via β-catenin-mediated protection of cerebral microvascular endothelial cells. Therefore, EMPA shows potential for improving stroke outcomes as an adjunctive preventive strategy.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"788-802"},"PeriodicalIF":10.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771508","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 mice to humans: advancing the path to cardioprotection.","authors":"Lina Badimon, Gemma Vilahur, Guiomar Mendieta","doi":"10.1093/cvr/cvaf048","DOIUrl":"10.1093/cvr/cvaf048","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"692-693"},"PeriodicalIF":10.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669212","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 paradigm shift in cardiovascular research: new method isolates intestinal interstitial fluid to understand gut microbiome and host cross-talk.","authors":"Fadi J Charchar, Francine Z Marques","doi":"10.1093/cvr/cvaf047","DOIUrl":"10.1093/cvr/cvaf047","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"697-698"},"PeriodicalIF":10.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718070","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":"Angiotensin 1-7 and a telomerase reverse transcriptase activator individually restore vasodilatory capacity within the human microcirculation previous SARS-CoV-2 infection.","authors":"Yoshinori Nishijima, Shelby N Hader, Erin C Birch, Yiliang Chen, Michael E Widlansky, Andreas M Beyer","doi":"10.1093/cvr/cvaf020","DOIUrl":"10.1093/cvr/cvaf020","url":null,"abstract":"","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"699-701"},"PeriodicalIF":10.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405702","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}