Basic Research in Cardiology最新文献

{"title":"The ketone body 3-hydroxybutyrate increases cardiac output and cardiac contractility in a porcine model of cardiogenic shock: a randomized, blinded, crossover trial","authors":"Oskar Kjærgaard Hørsdal, Alexander Møller Larsen, Kasper Lykke Wethelund, Frederik Flyvholm Dalsgaard, Jacob Marthinsen Seefeldt, Ole Kristian Lerche Helgestad, Niels Moeslund, Jacob Eifer Møller, Hanne Berg Ravn, Roni Ranghøj Nielsen, Henrik Wiggers, Kristoffer Berg-Hansen, Nigopan Gopalasingam","doi":"10.1007/s00395-025-01103-2","DOIUrl":"https://doi.org/10.1007/s00395-025-01103-2","url":null,"abstract":"<p>Cardiogenic shock (CS) is characterized by reduced cardiac output (CO), reduced end-organ perfusion, and high mortality. Medical therapies have failed to improve survival. The ketone body 3-hydroxybutyrate (3-OHB) enhances cardiac function in heart failure and CS. We aimed to elucidate the cardiovascular and cardiometabolic effects of 3-OHB treatment during CS. In a randomized, assessor-blinded crossover design, we studied 16 female pigs (60 kg, 5 months of age). CS was induced by left main coronary artery microsphere injections. Predefined criteria for CS were a 30% reduction in CO or mixed venous saturation (SvO₂). Intravenous 3-OHB infusion and a matching control solution were administered for 120 min in random order. Hemodynamic measurements were obtained by pulmonary artery catheterization and a left ventricular (LV) pressure–volume catheter. Myocardial mitochondrial function was assessed using high resolution respirometry. During CS, infusion with 3-OHB increased CO by 0.9 L/min (95%CI 0.4–1.3 L/min) compared with control infusion. SvO₂ (<i>P</i> = 0.026) and heart rate (<i>P</i> &lt; 0.001) increased. Stroke volume (<i>P</i> = 0.6) was not altered. LV contractile function as determined by LV end-systolic elastance improved during 3-OHB infusion compared with control infusion (<i>P</i> = 0.004). Systemic and pulmonary vascular resistance decreased, and diuresis increased. LV mitochondrial function was higher after 3-OHB infusion compared with control. We conclude that 3-OHB infusion enhances cardiac function by increasing contractility and reducing vascular resistance, while also preserving myocardial mitochondrial respiratory function in a large animal model of ischemic CS. These novel findings support the therapeutic potential of exogenous ketone supplementation in CS management.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"75 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822577","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":"Critical analysis of descriptive microRNA data in the translational research on cardioprotection and cardiac repair: lost in the complexity of bioinformatics","authors":"Mariann Gyöngyösi, Julia Guthrie, Ena Hasimbegovic, Emilie Han, Martin Riesenhuber, Kevin Hamzaraj, Jutta Bergler-Klein, Denise Traxler, Maximilian Y. Emmert, Matthias Hackl, Sophia Derdak, Dominika Lukovic","doi":"10.1007/s00395-025-01104-1","DOIUrl":"https://doi.org/10.1007/s00395-025-01104-1","url":null,"abstract":"<p>The unsuccessful translation of cardiac regeneration and cardioprotection from animal experiments to clinical applications in humans has raised the question of whether microRNA bioinformatics can narrow the gap between animal and human research outputs. We reviewed the literature for the period between 2000 and 2024 and found 178 microRNAs involved in cardioprotection and cardiac regeneration. On analyzing the orthologs and annotations, as well as downstream regulation, we observed species-specific differences in the diverse regulation of the microRNAs and related genes and transcriptomes, the influence of the experimental setting on the microRNA-guided biological responses, and database-specific bioinformatics results. We concluded that, in addition to reducing the number of in vivo experiments, following the 3R animal experiment rules, the bioinformatics approach allows the prediction of several currently unknown interactions between pathways, coding and non-coding genes, proteins, and downstream regulatory elements. However, a comprehensive analysis of the miRNA-mRNA-protein networks needs a profound bioinformatics and mathematical education and training to appropriately design an experimental study, select the right bioinformatics tool with programming language skills and understand and display the bioinformatics output of the results to translate the research data into clinical practice. In addition, using in-silico approaches, a risk of deviating from the in vivo processes exists, with adverse consequences on the translational research.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"43 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814111","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":"Exendin-4 improves cerebral ischemia by relaxing microvessels, rapidly increasing cerebral blood flow after reperfusion","authors":"Yujie Chen, Lei Wang, Yutong Zhou, Yuguang Wang, Wei Qin, Mingxiao Wang, Bo Liu, Qian Tian, Huisen Xu, Hui Shen, Chen Zheng","doi":"10.1007/s00395-025-01096-y","DOIUrl":"https://doi.org/10.1007/s00395-025-01096-y","url":null,"abstract":"<p>Intravenous thrombolysis remains the cornerstone for restoring cerebral reperfusion post-stroke. Despite recombinant tissue plasminogen activator (rtPA) achieving arterial reperfusion within 6 h, persistent microcirculatory blood flow reduction often hampers recovery. Exendin-4, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated potential for improving stroke outcomes, though its mechanisms remain partially unclear. This study investigated the role of Exendin-4 in restoring microcirculatory blood flow post-stroke. Using ischemic stroke models in 8-week-old male C57BL/6j mice, induced by transient middle cerebral artery occlusion or bilateral common carotid artery ligation, Exendin-4 (150 μg/kg) was administered intravenously. Infarct size and neurological deficits were evaluated using TTC staining and neurological severity scores. Real-time cerebral blood flow (CBF) and microvascular changes were measured with laser speckle imaging and two-photon microscopy. Mechanistic studies employed immunofluorescence and infrared differential interference contrast microscopy. Our findings demonstrated that Exendin-4 significantly reduced infarct size and improved neurological outcomes, independent of blood glucose levels. Immunofluorescence revealed GLP-1 receptor expression in arteriolar smooth muscle cells, endothelial cells, and pericytes. Exendin-4 enhanced microvascular blood flow via vasodilation, confirmed through real-time imaging. In vitro, Exendin-4 relaxed pre-constricted vessels, an effect that was abolished by eNOS and adenylate cyclase (AC) inhibitors. However, guanylate cyclase (GC) inhibition failed to block Exendin-4-induced vasodilation, suggesting a non-cGMP-dependent NO pathway may be involved. Furthermore, prostaglandin E2 (PGE2) signaling via EP4 receptors was identified as a critical contributor to Exendin-4’s vasodilatory effect, highlighting the involvement of multiple signaling pathways. These findings suggest that Exendin-4 preserves cerebral microcirculation through a multifaceted mechanism involving GLP-1R-mediated AC–cAMP signaling, PGE2–EP4 signaling, and a non-cGMP-dependent NO pathway. This study positions GLP-1 receptor agonists as promising therapeutic candidates for enhancing cerebral microcirculation and improving outcomes following stroke.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"70 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675217","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":"Necrosis-like cell death modes in heart failure: the influence of aetiology and the effects of RIP3 inhibition","authors":"Izabela Jarabicová, Csaba Horváth, Jaroslav Hrdlička, Almos Boroš, Veronika Olejníčková, Eva Zábrodská, Soňa Štemberková Hubáčková, Hana Mauer Šutovská, Ľuboš Molčan, Libor Kopkan, Martin Chudý, Branislav Kura, Barbora Kaločayová, Eva Goncalvesová, Jan Neckář, Michal Zeman, František Kolář, Adriana Adameová","doi":"10.1007/s00395-025-01101-4","DOIUrl":"https://doi.org/10.1007/s00395-025-01101-4","url":null,"abstract":"<p>Since cell dying in heart failure (HF) may vary based on the aetiology, we examined the main forms of regulated necrosis, such as necroptosis and pyroptosis, in the hearts damaged due to myocardial infarction (MI) or pressure overload. We also investigated the effects of a drug inhibiting RIP3, a proposed convergent point for both these necrosis-like cell death modes. In rat hearts, left ventricular function, remodelling, pro-cell death, and pro-inflammatory events were investigated, and the pharmacodynamic action of RIP3 inhibitor (GSK'872) was assessed. Regardless of the HF aetiology, the heart cells were dying due to necroptosis, albeit the upstream signals may be different. Pyroptosis was observed only in post-MI HF. The dysregulated miRNAs in post-MI hearts were accompanied by higher levels of a predicted target, HMGB1, its receptors (TLRs), as well as the exacerbation of inflammation likely originating from macrophages. The RIP3 inhibitor suppressed necroptosis, unlike pyroptosis, normalised the dysregulated miRNAs and tended to decrease collagen content and affect macrophage infiltration without affecting cardiac function or structure. The drug also mitigated the local heart inflammation and normalised the higher circulating HMGB1 in rats with post-MI HF. Elevated serum levels of HMGB1 were also detected in HF patients and positively correlated with C-reactive protein, highlighting pro-inflammatory axis. In conclusion, in MI-, but not pressure overload-induced HF, both necroptosis and pyroptosis operate and might underlie HF pathogenesis. The RIP3-targeting pharmacological intervention might protect the heart by preventing pro-death and pro-inflammatory mechanisms, however, additional strategies targeting multiple pro-death pathways may exhibit greater cardioprotection.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"23 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627500","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":"IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning","authors":"Sauri Hernandez-Resendiz, Reinis Vilskersts, David Aluja, Ioanna Andreadou, Péter Bencsik, Maija Dambrova, Panagiotis Efentakis, Fei Gao, Zoltán Giricz, Javier Inserte, Roisin Kelly-Laubscher, Attila Kiss, Thomas Krieg, Brenda R. Kwak, Sandrine Lecour, Gary Lopaschuk, Michał Mączewski, Michał Waszkiewicz, Marta Oknińska, Pasquale Pagliaro, Bruno Podesser, Hiran A. Prag, Marisol Ruiz-Meana, Tamara Szabados, Coert J. Zuurbier, Péter Ferdinandy, Derek J. Hausenloy","doi":"10.1007/s00395-025-01102-3","DOIUrl":"https://doi.org/10.1007/s00395-025-01102-3","url":null,"abstract":"<p>Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC). Eight sites from the COST Innovators Grant (IG16225) network participated in the IMPACT AMI study. Mice and rats were randomly allocated into Sham, Control, or IPC groups. The IRI group underwent 45 min (mice) or 30 min (rats) of left coronary artery occlusion followed by 24 h reperfusion. IPC comprised three cycles of 5 min occlusion/reperfusion before IRI. IS was determined by a blinded core lab. The majority of site showed significant cardioprotection with IPC. In pooled mouse data, IPC (<i>N</i> = 42) reduced IS/AAR by 35% compared to control (<i>N</i> = 48) (30 ± 16% versus 46 ± 13%; <i>p</i> &lt; 0.005), and in rat data, IPC (<i>N</i> = 36) reduced IS/AAR by 29% when compared to control (<i>N</i> = 39) (32 ± 19% versus 45 ± 14%; <i>p</i> &lt; 0.01). The IMPACT multisite mouse and rat AMI networks, with centralized randomization and blinded core IS analysis, were established to improve the reproducibility of cardioprotective interventions in preclinical studies and to facilitate the translation of these therapies for patient benefit.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"56 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599344","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":"Assessing customized multivalent chemokine-binding peptide treatment in a murine model of coxsackievirus B3 myocarditis","authors":"Nicolas Kelm, Meike Kespohl, Gintare Smagurauskaite, Serena Vales, Kalimuthu Karuppanan, Philomena Mburu, Arne Thiele, Sandra Pinkert, Thomas Bukur, Michael Mülleder, Nikolaus Berndt, Karin Klingel, Matthias M. Gaida, Shoumo Bhattacharya, Antje Beling","doi":"10.1007/s00395-025-01098-w","DOIUrl":"https://doi.org/10.1007/s00395-025-01098-w","url":null,"abstract":"<p>Myocarditis, an inflammatory disease of the heart muscle, is often triggered by viral infections. This inflammation, which can lead to severe cardiac dysfunction and adverse outcomes, is mediated by various CC and CXC chemokines that interact with receptors in a “one-to-many” fashion. Ticks have evolved chemokine-binding salivary proteins known as Evasins, which efficiently suppress inflammation. This study explores a tailored Evasin-derived CC chemokine-targeting strategy using a 17-mer synthetic dimeric peptide, BK1.3. This peptide inhibits the inflammatory chemokines CCL2, CCL3, CCL7, and CCL8 in murine Coxsackievirus B3 (CVB3) infection, a viral trigger of myocarditis. Administered at a dose of 5 mg/kg twice daily, BK1.3 effectively maintains virus control without exacerbating CVB3-induced morbidity markers, such as hemodynamic compromise, multiorgan failure with hepatitis and pancreatitis, hypothermia, hypoglycemia, and weight loss. Metabolic profiling combined with proteomics reveals preserved reprogramming of lipid storage and gluconeogenesis capacity in the liver, alongside sustained energy production in the injured heart muscle. In survivors of acute CVB3 infection exhibiting manifestations of the subacute phase, BK1.3 enhances virus control, reduces myeloid cell infiltration in the heart and liver, improves markers of liver injury, and alleviates cardiac dysfunction, as evidenced by echocardiographic global longitudinal strain analysis. These findings affirm the safety profile of BK1.3 peptide therapeutics in a preclinical mouse model of acute CVB3 infection and emphasize its potential for therapeutic advancement in addressing virus-induced inflammation in the heart.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"27 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495156","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":"Associations between female sex hormones, estrous cycle, ischemic preconditioning and myocardial infarct size after ischemia–reperfusion injury","authors":"Tetiana Pylova, Ahmed Elmahdy, Maryna Krasnikova, Abhishek Jha, Erik Axel Andersson, Yalda Kakaei, Aaron Shekka Espinosa, Amin Al-Awar, Ermir Zulfaj, Amirali Nejat, Valentyna Sevastianova, Mana Kalani, Henrik Ryberg, Åsa Tivesten, Elmir Omerovic, Björn Redfors","doi":"10.1007/s00395-025-01099-9","DOIUrl":"https://doi.org/10.1007/s00395-025-01099-9","url":null,"abstract":"<p>Studies on sex differences in myocardial infarction (MI) typically focus on males versus females, the exploration of hormonal physiologic variations and their impact on the infarct size remains limited. The objective of this study was to examine whether infarct size after myocardial ischemia/reperfusion injury in female rats differs in different phases of the estrous cycle, and according to the levels of sex hormones; and to assess whether the effect of ischemic preconditioning on infarct size varies in different phases of the estrous cycle and between sexes. Female rats were divided into three groups based on the estrous cycle: proestrus, estrus, and diestrus. A fourth group consisted of ovariectomized female rats. Male rats were included as a fifth group, and orchiectomized males as a sixth group. Each group underwent ischemia/reperfusion injury, with or without prior ischemic preconditioning (IPC). Plasma sex hormone levels were measured with gas chromatography-tandem mass spectrometry. Females in the proestrus showed significantly smaller infarct size compared to all other groups. Multivariable analyses identified proestrus, IPC, and estradiol as independent predictors of smaller infarct size while male sex and gonadectomy as independent predictors of larger infarct size. There was a statistical interaction between IPC and both sex and hormonal status, with a greater protective effect of IPC on infarct size in males and gonadectomized rats. After ischemia–reperfusion, proestrus female rats developed the smallest while male and gonadectomized rats the largest infarct size. Conversely, IPC conferred greater cardioprotection in male and gonadectomized rats than females in proestrus.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"7 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401933","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":"Evolocumab attenuates myocardial ischemia/reperfusion injury by blocking PCSK9/LIAS-mediated cuproptosis of cardiomyocytes","authors":"Zi-Zhuo Li, Lei Guo, Yan-Liang An, Wei-Jia Yu, Ding-Yu Shi, Qiu-Yue Lin, Bo Zhang","doi":"10.1007/s00395-025-01100-5","DOIUrl":"https://doi.org/10.1007/s00395-025-01100-5","url":null,"abstract":"<p>Myocardial ischemia‒reperfusion (I/R) injury is the crucial cause of poor prognosis after revascularization in patients with myocardial infarction (MI) due to the lack of specific therapeutic drugs. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is related to the pathogenesis and progression of various cardiovascular diseases. However, the specific role of PCSK9 in I/R-induced cardiac injury remains to be further investigated. In this study, wild-type (WT) C57BL/6J mice were administered evolocumab (a monoclonal antibody of PCSK9) before I/R surgery. Cardiac damage and function were assessed by echocardiography and TTC/Evans Blue staining. Inflammation, oxidative stress, mitochondrial dysfunction, and cuproptosis were evaluated by histopathology and qPCR. The interaction between proteins was confirmed by protein docking and co-immunoprecipitation. Our data revealed that PCSK9 level was increased in I/R-induced mouse serum and hearts and in serum of MI patients. Furthermore, evolocumab significantly improved cardiac injury and dysfunction, inflammation, oxidative stress, and cuproptosis. Mechanistically, evolocumab obstructs the direct interaction of PCSK9 and LIAS, and subsequently inhibits cardiomyocyte cuproptosis. In conclusion, inhibition of PCSK9 alleviates I/R-induced cardiac remodeling and dysfunction by targeting LIAS-mediated cuproptosis, which may be a novel therapeutic strategy for patients with ischemic cardiomyopathy.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"29 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385124","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 role and mechanism of epigenetics in anticancer drug-induced cardiotoxicity.","authors":"Xuening Liu, Zijian Li","doi":"10.1007/s00395-024-01054-0","DOIUrl":"10.1007/s00395-024-01054-0","url":null,"abstract":"<p><p>Cardiovascular disease is the main factor contributing to the global burden of diseases, and the cardiotoxicity caused by anticancer drugs is an essential component that cannot be ignored. With the development of anticancer drugs, the survival period of cancer patients is prolonged; however, the cardiotoxicity caused by anticancer drugs is becoming increasingly prominent. Currently, cardiovascular disease has emerged as the second leading cause of mortality among long-term cancer survivors. Anticancer drug-induced cardiotoxicity has become a frontier and hot topic. The discovery of epigenetics has given the possibility of environmental changes in gene expression, protein synthesis, and traits. It has been found that epigenetics plays a pivotal role in promoting cardiovascular diseases, such as heart failure, coronary heart disease, and hypertension. In recent years, increasing studies have underscored the crucial roles played by epigenetics in anticancer drug-induced cardiotoxicity. Here, we provide a comprehensive overview of the role and mechanisms of epigenetics in anticancer drug-induced cardiotoxicity.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"11-24"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897246","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":"Molecular fingerprints of cardiovascular toxicities of immune checkpoint inhibitors.","authors":"Tamás G Gergely, Zsófia D Drobni, Nabil V Sayour, Péter Ferdinandy, Zoltán V Varga","doi":"10.1007/s00395-024-01068-8","DOIUrl":"10.1007/s00395-024-01068-8","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by unleashing the power of the immune system against malignant cells. However, their use is associated with a spectrum of adverse effects, including cardiovascular complications, which can pose significant clinical challenges. Several mechanisms contribute to cardiovascular toxicity associated with ICIs. First, the dysregulation of immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1) and its ligand (PD-L1), and molecular mimicry with cardiac autoantigens, leads to immune-related adverse events, including myocarditis and vasculitis. These events result from the aberrant activation of T cells against self-antigens within the myocardium or vascular endothelium. Second, the disruption of immune homeostasis by ICIs can lead to autoimmune-mediated inflammation of cardiac tissues, manifesting as cardiac dysfunction and heart failure, arrhythmias, or pericarditis. Furthermore, the upregulation of inflammatory cytokines, particularly tumor necrosis factor-alpha, interferon-γ, interleukin-1β, interleukin-6, and interleukin-17 contributes to cardiac and endothelial dysfunction, plaque destabilization, and thrombosis, exacerbating cardiovascular risk on the long term. Understanding the intricate mechanisms of cardiovascular side effects induced by ICIs is crucial for optimizing patient care and to ensure the safe and effective integration of immunotherapy into a broader range of cancer treatment protocols. The clinical implications of these mechanisms underscore the importance of vigilant monitoring and early detection of cardiovascular toxicity in patients receiving ICIs. Future use of these key pathological mediators as biomarkers may aid in prompt diagnosis of cardiotoxicity and will allow timely interventions.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"187-205"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632513","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}