{"title":"Functional diversity of cardiac macrophages in health and disease","authors":"Steven Yang, Vinay Penna, Kory J. Lavine","doi":"10.1038/s41569-024-01109-8","DOIUrl":"https://doi.org/10.1038/s41569-024-01109-8","url":null,"abstract":"<p>Macrophages make up a substantial portion of the stromal compartment of the heart in health and disease. In the past decade, the origins of these cardiac macrophages have been established as two broad populations derived from either embryonic or definitive haematopoiesis and that can be distinguished by the expression of CC-motif chemokine receptor 2 (CCR2). These cardiac macrophage populations are transcriptionally distinct and have differing cell surface markers and divergent roles in cardiac homeostasis and disease. Embryonic-derived CCR2<sup>−</sup> macrophages are a tissue-resident population that participates in tissue development, repair and maintenance, whereas CCR2<sup>+</sup> macrophages are derived from definitive haematopoiesis and contribute to inflammation and tissue damage. Studies from the past 5 years have leveraged single-cell RNA sequencing technologies to expand our understanding of cardiac macrophage diversity, particularly of the monocyte-derived macrophage populations that reside in the injured and diseased heart. Emerging technologies in spatial transcriptomics have enabled the identification of distinct disease-associated cellular neighbourhoods consisting of macrophages, other immune cells and fibroblasts, highlighting the involvement of macrophages in cell–cell communication. Together, these discoveries lend new insights into the role of specific macrophage populations in the pathogenesis of cardiac disease, which can pave the way for the identification of new therapeutic targets and the development of diagnostic tools. In this Review, we discuss the developmental origin of cardiac macrophages and describe newly identified cell states and associated cellular neighbourhoods in the steady state and injury settings. We also discuss various contributions and effector functions of cardiac macrophages in homeostasis and disease.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"29 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911514","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 spleen in ischaemic heart disease","authors":"Gerd Heusch, Petra Kleinbongard","doi":"10.1038/s41569-024-01114-x","DOIUrl":"https://doi.org/10.1038/s41569-024-01114-x","url":null,"abstract":"<p>Ischaemic heart disease is a consequence of coronary atherosclerosis, and atherosclerosis is a systemic inflammatory disease. The spleen releases various immune cells in temporally distinct patterns. Neutrophils, monocytes, macrophages, B cells and T cells execute innate and adaptive immune processes in the coronary atherosclerotic plaque and in the ischaemic myocardium. Prolonged inflammation contributes to ischaemic heart failure. The spleen is also a target of neuromodulation through vagal, sympathetic and sensory nerve activation. Efferent vagal activation and subsequent activation of the noradrenergic splenic nerve activate β<sub>2</sub>-adrenergic receptors on splenic T cells, which release acetylcholine that ultimately results in attenuation of cytokine secretion from splenic macrophages. Coeliac vagal nerve activation increases splenic sympathetic nerve activity and drives the release of T cells, a process that depends on placental growth factor. Activation of the vagosplenic axis protects acutely from ischaemia–reperfusion injury during auricular tragus vagal stimulation and remote ischaemic conditioning. Splenectomy abrogates all these deleterious and beneficial actions on the cardiovascular system. The aggregate effect of splenectomy in humans is a long-term increase in mortality from ischaemic heart disease. The spleen has been appreciated as an important immune organ for inflammatory processes in atherosclerosis, myocardial infarction and heart failure, whereas its complex interaction with circulating blood factors and with the autonomic and somatic nervous systems, as well as its role in cardioprotection, have emerged only in the past decade. In this Review, we describe this newly identified cardioprotective function of the spleen and highlight the potential for translating the findings to patients with ischaemic heart disease.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"38 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911520","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":"Renal denervation for hypertension","authors":"Naomi D. L. Fisher, Ajay J. Kirtane","doi":"10.1038/s41569-024-01104-z","DOIUrl":"https://doi.org/10.1038/s41569-024-01104-z","url":null,"abstract":"<p>Innovative therapies for hypertension are desperately needed given the rising prevalence and falling rates of control of hypertension despite an abundance of available medical therapies. Procedural interventions lower blood pressure without depending on adherence to medications, and endovascular renal denervation (RDN) is the interventional procedure with the best evidence base for the treatment of hypertension. After nearly two decades of study, with major refinements to devices, technique and trial design, two different systems for RDN received approval from the FDA in late 2023 for the treatment of hypertension. These decisions were based on a portfolio of sham-controlled clinical trials demonstrating efficacy and safety of both radiofrequency and ultrasound RDN in treating patients across the spectrum of hypertension, including patients with mild disease taking no or one medication as well as those with moderate and truly resistant hypertension. In this Review, we begin by summarizing the background and scope of the global problem of hypertension control and explore the evolution and mechanism of RDN. We then detail early studies and randomized clinical trials demonstrating the efficacy and safety of RDN procedures, review international statements, and provide practical guidance on patient selection and implementation of RDN, including the crucial aspects of building a hypertension team and of involving patients in shared decision-making.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"1 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911510","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":"Haematometabolism rewiring in atherosclerotic cardiovascular disease","authors":"Laurent Yvan-Charvet, Thibault Barouillet, Coraline Borowczyk","doi":"10.1038/s41569-024-01108-9","DOIUrl":"https://doi.org/10.1038/s41569-024-01108-9","url":null,"abstract":"<p>Atherosclerotic cardiovascular diseases are the most frequent cause of death worldwide. The clinical complications of atherosclerosis are closely linked to the haematopoietic and immune systems, which maintain homeostatic functions and vital processes in the body. The nodes linking metabolism and inflammation are receiving increasing attention because they are inextricably linked to inflammatory manifestations of non-communicable diseases, including atherosclerosis. Although metabolism and inflammation are essential to survival and involve all tissues, we still know little about how these processes influence each other. In an effort to understand these mechanisms, in this Review we explore whether and how potent cardiovascular risk factors and metabolic modifiers of atherosclerosis influence the molecular and cellular machinery of ‘haematometabolism’ (metabolic-dependent haematopoietic stem cell skewing) and ‘efferotabolism’ (metabolic-dependent efferocyte reprogramming). These changes might ultimately propagate a quantitative and qualitative drift of the macrophage supply chain and affect the clinical manifestations of atherosclerosis. Refining our understanding of the different metabolic requirements of these processes could open the possibility of developing therapeutics targeting haematometabolism that, in conjunction with improved dietary habits, help rebalance and promote efficient haematopoiesis and efferocytosis and decrease the risk of atherosclerosis complications.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"67 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911512","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":"Extracellular matrix in vascular homeostasis and disease","authors":"Lu Zhang, Jing Zhou, Wei Kong","doi":"10.1038/s41569-024-01103-0","DOIUrl":"https://doi.org/10.1038/s41569-024-01103-0","url":null,"abstract":"<p>The extracellular matrix is an essential component and constitutes a dynamic microenvironment of the vessel wall with an indispensable role in vascular homeostasis and disease. From early development through to ageing, the vascular extracellular matrix undergoes various biochemical and biomechanical alterations in response to diverse environmental cues and exerts precise regulatory control over vessel remodelling. Advances in novel technologies that enable the comprehensive evaluation of extracellular matrix components and cell–matrix interactions have led to the emergence of therapeutic strategies that specifically target this fine-tuned network. In this Review, we explore various aspects of extracellular matrix biology in vascular development, disorders and ageing, emphasizing the effect of the extracellular matrix on disease initiation and progression. Additionally, we provide an overview of the potential therapeutic implications of targeting the extracellular matrix microenvironment in vascular diseases.</p>","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"16 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911508","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 macrophage–fibroblast interactions in the failing heart","authors":"Nikolaos G. Frangogiannis","doi":"10.1038/s41569-024-01112-z","DOIUrl":"https://doi.org/10.1038/s41569-024-01112-z","url":null,"abstract":"Macrophage–fibroblast interactions have a central role in cardiac fibrosis. In response to left ventricular pressure overload, CCR2+ cardiac macrophages acquire a fibrogenic phenotype, secreting IL-1β and promoting the activation of a FAP+ POSTN+ fibroblast subpopulation through the transcription factor MEOX1. Macrophage-derived fibroblast-activating cytokines (such as IL-1β), growth factors and matricellular proteins contribute to the pathogenesis of heart failure.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"12 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831959","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":"Left atrial appendage closure after ablation: the best OPTION for patients with AF?","authors":"Karina Huynh","doi":"10.1038/s41569-024-01113-y","DOIUrl":"10.1038/s41569-024-01113-y","url":null,"abstract":"Two studies presented at AHA 2024 Scientific Sessions describe the efficacy and safety of left atrial appendage closure after catheter ablation for atrial fibrillation and the 5-year outcomes of the largest randomized left atrial appendage closure trial to date comparing the safety and efficacy of two devices.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 2","pages":"67-67"},"PeriodicalIF":41.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809728","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}
Pietro Enea Lazzerini, Riccardo Accioli, Pier Leopoldo Capecchi, Maurizio Acampa
{"title":"Pro-arrhythmic potential of proton-pump inhibitors","authors":"Pietro Enea Lazzerini, Riccardo Accioli, Pier Leopoldo Capecchi, Maurizio Acampa","doi":"10.1038/s41569-024-01107-w","DOIUrl":"https://doi.org/10.1038/s41569-024-01107-w","url":null,"abstract":"Population studies have reported that proton-pump inhibitors (PPIs) increase cardiovascular mortality, at least in part owing to an increased propensity for life-threatening arrhythmias, but these findings have largely been ignored. We propose a series of recommendations for prescribers of PPIs to ensure a balance of the benefits against the potential arrhythmic risks.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"93 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797040","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":"Unlocking excellence in health care: the power of inclusive and sensitive language in medicine","authors":"Sarah M. Birkhoelzer, Sonia S. Anand","doi":"10.1038/s41569-024-01101-2","DOIUrl":"10.1038/s41569-024-01101-2","url":null,"abstract":"This call to action aims to increase awareness of inclusive language in medicine to enhance the experiences of patients and staff and improve health outcomes. Recognizing that terms change, we urge all health-care professionals to advocate for their colleagues and patients. This responsibility to educate the community should not fall exclusively onto marginalized communities.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 3","pages":"139-140"},"PeriodicalIF":41.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673280","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":"Charting the future of cardiology with large language model artificial intelligence","authors":"Ramsey M. Wehbe","doi":"10.1038/s41569-024-01105-y","DOIUrl":"10.1038/s41569-024-01105-y","url":null,"abstract":"Large language models represent a transformative leap in artificial intelligence and natural language processing, offering exciting potential across cardiology, from clinical care to education and research. However, several crucial challenges limit the practical implementation of large language models in cardiology. Interdisciplinary research is imperative to overcome these barriers.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"22 3","pages":"143-144"},"PeriodicalIF":41.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142670677","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}