Basic Research in Cardiology最新文献

{"title":"Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy.","authors":"Florian Buehning, Tobias Lerchner, Julia Vogel, Ulrike B Hendgen-Cotta, Matthias Totzeck, Tienush Rassaf, Lars Michel","doi":"10.1007/s00395-024-01070-0","DOIUrl":"10.1007/s00395-024-01070-0","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI) therapy represents a ground-breaking paradigm in cancer treatment, harnessing the immune system to combat malignancies by targeting checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The use of ICI therapy generates distinctive immune-related adverse events (irAEs) including cardiovascular toxicity, necessitating targeted research efforts. This comprehensive review explores preclinical models dedicated to ICI-mediated cardiovascular complications including myocarditis. Tailored preclinical models of ICI-mediated myocardial toxicities highlight the key role of CD8⁺ T cells, emphasizing the profound impact of immune checkpoints on maintaining cardiac integrity. Cytokines and macrophages were identified as possible driving factors in disease progression, and at the same time, initial data on possible cardiac antigens responsible are emerging. The implications of contributing factors including thoracic radiation, autoimmune disorder, and the presence of cancer itself are increasingly understood. Besides myocarditis, mouse models unveiled an accelerated progression of atherosclerosis, adding another layer for a thorough understanding of the diverse processes involving cardiovascular immune checkpoint signalling. This review aims to discuss current preclinical models of ICI cardiotoxicity and their potential for improving enhanced risk assessment and diagnostics, offering potential targets for innovative cardioprotective strategies. Lessons from ICI therapy can drive novel approaches in cardiovascular research, extending insights to areas such as myocardial infarction and heart failure.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"171-185"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750195","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":"Bridging cardiology and oncology in the era of precision medicine.","authors":"Tienush Rassaf","doi":"10.1007/s00395-025-01097-x","DOIUrl":"10.1007/s00395-025-01097-x","url":null,"abstract":"","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"120 1","pages":"1-2"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078517","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":"Cardioprotection strategies for anthracycline cardiotoxicity.","authors":"Andrea Moreno-Arciniegas, Laura Cádiz, Carlos Galán-Arriola, Agustín Clemente-Moragón, Borja Ibáñez","doi":"10.1007/s00395-024-01078-6","DOIUrl":"10.1007/s00395-024-01078-6","url":null,"abstract":"<p><p>Thanks to the fantastic progress in cancer therapy options, there is a growing population of cancer survivors. This success has resulted in a need to focus much effort into improving the quality of life of this population. Cancer and cardiovascular disease share many common risk factors and have an interplay between them, with one condition mechanistically affecting the other and vice versa. Furthermore, widely prescribed cancer therapies have known toxic effects in the cardiovascular system. Anthracyclines are the paradigm of efficacious cancer therapy widely prescribed with a strong cardiotoxic potential. While some cancer therapies cardiovascular toxicities are transient, others are irreversible. There is a growing need to develop cardioprotective therapies that, when used in conjunction with cancer therapies, can prevent cardiovascular toxicity and thus improve long-term quality of life in survivors. The field has three main challenges: (i) identification of the ultimate mechanisms leading to cardiotoxicity to (ii) identify specific therapeutic targets, and (iii) more sensible diagnostic tools to early identify these conditions. In this review we will focus on the cardioprotective strategies tested and under investigation. We will focus this article into anthracycline cardiotoxicity since it is still the agent most widely prescribed, the one with higher toxic effects on the heart, and the most widely studied.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"71-90"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153083","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":"Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients.","authors":"Giuseppe Panuccio, Pierpaolo Correale, Maria d'Apolito, Luciano Mutti, Rocco Giannicola, Luigi Pirtoli, Antonio Giordano, Demetrio Labate, Sebastiano Macheda, Nicole Carabetta, Youssef S Abdelwahed, Ulf Landmesser, Pierfrancesco Tassone, Pierosandro Tagliaferri, Salvatore De Rosa, Daniele Torella","doi":"10.1007/s00395-024-01077-7","DOIUrl":"10.1007/s00395-024-01077-7","url":null,"abstract":"<p><p>Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"153-169"},"PeriodicalIF":7.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118893","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":"Intravenous and oral administration of the synthetic RNA drug, TY1, reverses heart failure with preserved ejection fraction in mice","authors":"Kazutaka Miyamoto, Xaviar M. Jones, Shukuro Yamaguchi, Alessandra Ciullo, Chang Li, Joshua Godoy Coto, Kara Tsi, Jessica Anderson, Ashley Morris, Eduardo Marbán, Ahmed Gamal-Eldin Ibrahim","doi":"10.1007/s00395-024-01095-5","DOIUrl":"https://doi.org/10.1007/s00395-024-01095-5","url":null,"abstract":"<p>TY1, a synthetic non-coding RNA (ncRNA) bioinspired by small Y RNAs abundant in extracellular vesicles (EVs), decreases cGAS/STING activation in myocardial infarction and thereby attenuates inflammation. Motivated by the concept that heart failure with preserved ejection fraction (HFpEF) is a systemic inflammatory disease, we tested TY1 in a murine model of HFpEF. Intravenous TY1, packaged in a transfection reagent, reversed the cardiac and systemic manifestations of HFpEF in two-hit obese-hypertensive mice, without inducing weight loss. The effects of TY1 were specific, insofar as they were not reproduced by a control RNA of the same nucleotide content but in scrambled order. TY1 consistently suppressed myocardial stress-induced MAP kinase signaling, as well as downstream inflammatory, fibrotic, and hypertrophic gene pathways in heart tissue. TY1 not only prevented but actually reversed key pathological processes underlying HFpEF, with no evidence of toxicity. Most noteworthy from a practical perspective, the effects of intravenous TY1 were reproduced by feeding HFpEF mice an oral micellar formulation of TY1. As the prototype for a novel class of ncRNA drugs which target cell stress, TY1 exhibits exceptional disease-modifying bioactivity in HFpEF.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"1 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905107","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":"High-resolution DNA methylation changes reveal biomarkers of heart failure with preserved ejection fraction versus reduced ejection fraction","authors":"Giuditta Benincasa, Mark E. Pepin, Vincenzo Russo, Francesco Cacciatore, Michele D’Alto, Paola Argiento, Emanuele Romeo, Rosaria Chiappetti, Nunzia Laezza, Adam R. Wende, Gabriele G. Schiattarella, Enrico Coscioni, Antonietta La Montagna, Cristiano Amarelli, Ciro Maiello, Paolo Golino, Gianluigi Condorelli, Claudio Napoli","doi":"10.1007/s00395-024-01093-7","DOIUrl":"https://doi.org/10.1007/s00395-024-01093-7","url":null,"abstract":"<p>Novel biomarkers are needed to better identify—and distinguish—heart failure with preserved ejection fraction (HFpEF) from other clinical phenotypes. The goal of our study was to identify epigenetic-sensitive biomarkers useful to a more accurate diagnosis of HFpEF. We performed a network-oriented genome-wide DNA methylation study of circulating CD4⁺ T lymphocytes isolated from peripheral blood using reduced representation bisulfite sequencing (RRBS) in two cohorts (i.e., discovery/validation) each of both male and female patients with HFpEF (<i>n</i> = 12/10), HF with reduced EF (HFrEF; <i>n</i> = 7/5), and volunteers lacking clinical evidence of HF (CON; <i>n</i> = 7/5). RRBS is the gold-standard platform for measuring genome-wide DNA methylation changes at single-cytosine resolution in hypothesis-generating studies. We identified three hypomethylated HFpEF-specific differentially methylated positions (DMPs) associated with <i>FOXB1</i>, <i>ELMOD1</i>, and <i>DGKH</i> genes wherein ROC curve analysis revealed that increased expression levels had a reasonable diagnostic performance in predicting HFpEF (AUC ≥ 0.8, <i>p</i> &lt; 0.05). Network analysis identified additional three genes including <i>JUNB</i> (<i>p</i> = 0.037)<i>, SETD7</i> (<i>p</i> = 0.003)<i>,</i> and <i>MEF2D</i> (<i>p</i> = 0.0001) which were significantly higher in HFpEF <i>vs</i>. HFrEF patients. ROC curve analysis showed that integrating the functional H₂FPEF classification with the expression levels of the <i>FOXB1</i>, <i>ELMOD1</i>, and <i>DGKH</i> as well as the <i>JUNB</i>, <i>SETD7</i>, and <i>MEF2D</i> genes improved diagnostic accuracy, with AUC = 0.8 (<i>p</i> &lt; 0.0001) as compared to H₂FPEF score alone (<i>p</i> &gt; 0.05). Besides, increased expression levels of <i>SETD7-RELA-IL6</i> axis significantly discriminated overweight/obese HFpEF vs. HFrEF patients (AUC = 1; <i>p</i> = 0.001, <i>p</i> = 0.006, <i>p</i> = 0.006, respectively). We support an emerging dogma that indirect epigenetic testing via high-resolution RRBS methylomics represents a non-invasive tool that may enable easier access to both diagnostic and mechanistic insights of HFpEF. An epigenetic-oriented dysregulation of network-derived <i>SETD7-RELA-IL6</i> axis in circulating CD4⁺ T lymphocytes may drive pro-inflammatory responses which, in turn, may lead to cardiac remodeling in overweight/obese HFpEF.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"15 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887490","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":"Inter-organ communication: pathways and targets to cardioprotection and neuro-protection. A report from the 12th Hatter Cardiovascular Institute workshop","authors":"L. Pearce, C. Galán-Arriola, R. M. Bell, R. D. Carr, J. Cunningham, S. M. Davidson, A. K. Ghosh, S. Giesz, P. Golforoush, A. V. Gourine, D. M. Hermann, G. Heusch, B. Ibanez, S. Beikoghli Kalkhoran, S. Lecour, K. Lukhna, M. Ntsekhe, M. N. Sack, R. J. Unwin, G. Vilahur, J. M. Walker, D. M. Yellon","doi":"10.1007/s00395-024-01094-6","DOIUrl":"https://doi.org/10.1007/s00395-024-01094-6","url":null,"abstract":"<p>A long-standing aim in the setting of various pathologies including acute myocardial infarction, chronic kidney disease (CKD), and ischaemic stroke, has been to identify successful approaches to augment cellular and organ protection. Although the continual evolution and refinement of ideas over the past few decades has allowed the field to progress, we are yet to realise successful clinical translation of this concept. The 12th Hatter Cardiovascular Workshop identified a number of important points and key questions for future research relating to cardio- and neuro-protection and interorgan communication. Specific topics that were discussed include the ‘cardio-metabolic-renal’ axis of organ protection, the parasympathetic signalling hypothesis, the role of the coronary microvasculature in myocardial infarction, the RISK pathway of cardioprotection, extracellular vesicles and the way forward, the future for clinical studies of remote ischaemic conditioning, and new experimental models for cardio-oncology investigations.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"30 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831958","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":"Changes in tumor and cardiac metabolism upon immune checkpoint","authors":"Anna-Sophia Leven, Natalie Wagner, Stephan Nienaber, Daniel Messiha, Alpaslan Tasdogan, Selma Ugurel","doi":"10.1007/s00395-024-01092-8","DOIUrl":"https://doi.org/10.1007/s00395-024-01092-8","url":null,"abstract":"<p>Cardiovascular disease and cancer are the leading causes of death in the Western world. The associated risk factors are increased by smoking, hypertension, diabetes, sedentary lifestyle, aging, unbalanced diet, and alcohol consumption. Therefore, the study of cellular metabolism has become of increasing importance, with current research focusing on the alterations and adjustments of the metabolism of cancer patients. This may also affect the efficacy and tolerability of anti-cancer therapies such as immune-checkpoint inhibition (ICI). This review will focus on metabolic adaptations and their consequences for various cell types, including cancer cells, cardiac myocytes, and immune cells. Focusing on ICI, we illustrate how anti-cancer therapies interact with metabolism. In addition to the desired tumor response, we highlight that ICI can also lead to a variety of side effects that may impact metabolism or vice versa. With regard to the cardiovascular system, ICI-induced cardiotoxicity is increasingly recognized as one of the most life-threatening adverse events with a mortality of up to 50%. As such, significant efforts are being made to assess the specific interactions and associated metabolic changes associated with ICIs to improve both efficacy and management of side effects.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"47 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804780","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 cardio-oncologic burden of breast cancer: molecular mechanisms and importance of preclinical models","authors":"J. Brauer, M. Tumani, N. Frey, L. H. Lehmann","doi":"10.1007/s00395-024-01090-w","DOIUrl":"https://doi.org/10.1007/s00395-024-01090-w","url":null,"abstract":"<p>Breast cancer, the most prevalent cancer affecting women worldwide, poses a significant cardio-oncological burden. Despite advancements in novel therapeutic strategies, anthracyclines, HER2 antagonists, and radiation remain the cornerstones of oncological treatment. However, each carries a risk of cardiotoxicity, though the molecular mechanisms underlying these adverse effects differ. Common mechanisms include DNA damage response, increased reactive oxygen species, and mitochondrial dysfunction, which are key areas of ongoing research for potential cardioprotective strategies. Since these mechanisms are also essential for effective tumor cytotoxicity, we explore tumor-specific effects, particularly in hereditary breast cancer linked to BRCA1 and BRCA2 mutations. These genetic variants impair DNA repair mechanisms, increase the risk of tumorigenesis and possibly for cardiotoxicity from treatments such as anthracyclines and HER2 antagonists. Novel therapies, including immune checkpoint inhibitors, are used in the clinic for triple-negative breast cancer and improve the oncological outcomes of breast cancer patients. This review discusses the molecular mechanisms underlying BRCA dysfunction and the associated pathological pathways. It gives an overview of preclinical models of breast cancer, such as genetically engineered mouse models, syngeneic murine models, humanized mouse models, and various in vitro and ex vivo systems and models to study cardiovascular side effects of breast cancer therapies. Understanding the underlying mechanism of cardiotoxicity and developing cardioprotective strategies in preclinical models are essential for improving treatment outcomes and reducing long-term cardiovascular risks in breast cancer patients.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":"16 1","pages":""},"PeriodicalIF":9.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758497","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":"Proprioceptors of the human pericardium.","authors":"Lea M Piermaier, Svenja Caspers, Christina Herold, Michael Wolf-Vollenbröker, Patrick Brzoska, Eric Bechler, Timm J Filler","doi":"10.1007/s00395-024-01075-9","DOIUrl":"10.1007/s00395-024-01075-9","url":null,"abstract":"<p><p>In the human organism, all functions are regulated and, therefore, require a feedback mechanism. This control involves a perception of the spatial tensile state of cardiac tissues. The presence and distribution of respective proprioceptive corpuscles have not been considered so far. Therefore, a comprehensive study of the entire human fibrous pericardium was conducted to describe the presence of proprioceptors, their density, and distribution patterns. Eight human pericardial specimens gained from our body donation program were used to create a three-dimensional map of proprioceptors in the pericardium based on their histological and immunohistochemical identification. The 3D map was generated as a volume-rendered 3D model based on magnetic resonance imaging of the pericardium, to which all identified receptors were mapped. To discover a systematic pattern in receptor distribution, statistical cluster analysis was conducted using the Scikit-learn library in Python. Ruffini-like corpuscles (RLCs) were found in all pericardia and assigned to three histological receptor localizations depending on the fibrous pericardium's layering, with no other corpuscular proprioceptors identified. Cluster analysis revealed that RLCs exhibit a specific topographical arrangement. The highest receptor concentrations occur at the ventricular bulges, where their size reaches its maximum in terms of diameter, and at the perivascular pericardial turn-up. The findings suggest that the pericardium is subject to proprioceptive control. RLCs record lateral shearing between the pericardial sublayers, and their distribution pattern enables the detection of distinct dilatation of the heart. Therefore, the pericardium might have an undiscovered function as a sensor with the RLCs as its anatomical correlate.</p>","PeriodicalId":8723,"journal":{"name":"Basic Research in Cardiology","volume":" ","pages":"1029-1043"},"PeriodicalIF":7.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11628447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905784","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}