Nature Reviews Cardiology最新文献_第2页

Mechano-energetic uncoupling in heart failure 心力衰竭的机械-能量解耦

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-22 DOI: 10.1038/s41569-025-01167-6

Dunja Aksentijevic, Simon Sedej, Jeremy Fauconnier, Melanie Paillard, Mahmoud Abdellatif, Katrin Streckfuss-Bömeke, Renée Ventura-Clapier, Jolanda van der Velden, Rudolf A. de Boer, Edoardo Bertero, Jan Dudek, Vasco Sequeira, Christoph Maack

{"title":"Mechano-energetic uncoupling in heart failure","authors":"Dunja Aksentijevic, Simon Sedej, Jeremy Fauconnier, Melanie Paillard, Mahmoud Abdellatif, Katrin Streckfuss-Bömeke, Renée Ventura-Clapier, Jolanda van der Velden, Rudolf A. de Boer, Edoardo Bertero, Jan Dudek, Vasco Sequeira, Christoph Maack","doi":"10.1038/s41569-025-01167-6","DOIUrl":"https://doi.org/10.1038/s41569-025-01167-6","url":null,"abstract":"Heart failure (HF) is a major global and life-threatening disease. Despite advances in therapies, the prevalence of HF is increasing owing to an ageing population and the pervasive pandemic of obesity and metabolic disorders, which have transformed the pathophysiology of HF. Changes in cardiac energy metabolism and the related energy deficit crucially contribute to the severity and type of HF. Furthermore, perturbations in excitation–contraction coupling, mitochondrial function and oxidative stress are characteristic features of HF. In this Review, we focus on the close interaction between cardiac mechanics and mitochondrial energetics, and decipher how this mechano-energetic coupling is disturbed in various acquired and hereditary forms of HF. In HF with reduced ejection fraction, defects in excitation–contraction coupling are key drivers of mechano-energetic uncoupling, whereas in HF with preserved ejection fraction, increased preload and afterload imposed by obesity, hypertension and age-dependent vascular stiffness increase mechanical workload, which is insufficiently matched by mitochondrial tricarboxylic acid cycle activity and ATP supply. In both scenarios, oxidative stress results from depletion of the antioxidative capacity and contributes to maladaptive cardiac remodelling and dysfunction. Several established and emerging treatments for HF target this mechano-energetic uncoupling, and a greater understanding of the underlying mechanisms will open new therapeutic opportunities to alleviate the burden of HF.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"15 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337508","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}

引用次数: 0

Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets. 心力衰竭的心脏中间代谢：底物使用，信号作用和治疗靶点。

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-22 DOI: 10.1038/s41569-025-01166-7

Mathias Mericskay,Coert J Zuurbier,Lisa C Heather,Anja Karlstaedt,Javier Inserte,Luc Bertrand,Georgios Kararigas,Marisol Ruiz-Meana,Christoph Maack,Gabriele G Schiattarella

{"title":"Cardiac intermediary metabolism in heart failure: substrate use, signalling roles and therapeutic targets.","authors":"Mathias Mericskay,Coert J Zuurbier,Lisa C Heather,Anja Karlstaedt,Javier Inserte,Luc Bertrand,Georgios Kararigas,Marisol Ruiz-Meana,Christoph Maack,Gabriele G Schiattarella","doi":"10.1038/s41569-025-01166-7","DOIUrl":"https://doi.org/10.1038/s41569-025-01166-7","url":null,"abstract":"The number of patients with heart failure is expected to rise sharply owing to ageing populations, poor dietary habits, unhealthy lifestyles and improved survival rates from conditions such as hypertension and myocardial infarction. Heart failure is classified into two main types: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). These forms fundamentally differ, especially in how metabolism is regulated, but they also have shared features such as mitochondrial dysfunction. HFrEF is typically driven by neuroendocrine activation and mechanical strain, which demands a higher ATP production to sustain cardiac contraction. However, the primary energy source in a healthy heart (fatty acid β-oxidation) is often suppressed in HFrEF. Although glucose uptake increases in HFrEF, mitochondrial dysfunction disrupts glucose oxidation, and glycolysis and ketone oxidation only partially compensate for this imbalance. Conversely, HFpEF, particularly in individuals with metabolic diseases, such as obesity or type 2 diabetes mellitus, results from both mechanical and metabolic overload. Elevated glucose and lipid levels overwhelm normal metabolic pathways, leading to an accumulation of harmful metabolic byproducts that impair mitochondrial and cellular function. In this Review, we explore how disruptions in cardiac metabolism are not only markers of heart failure but also key drivers of disease progression. We also examine how metabolic intermediates influence signalling pathways that modify proteins and regulate gene expression in the heart. The growing recognition of the role of metabolic alterations in heart failure has led to groundbreaking treatments that target these metabolic disruptions, offering new hope for these patients.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"8 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337472","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}

引用次数: 0

Metabolic alterations in heart failure 心力衰竭的代谢改变

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-22 DOI: 10.1038/s41569-025-01181-8

Christoph Maack

引用次数: 0

Immunometabolism in heart failure 心力衰竭的免疫代谢

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-22 DOI: 10.1038/s41569-025-01165-8

Ioanna Andreadou, Alessandra Ghigo, Panagiota-Efstathia Nikolaou, Filip K. Swirski, James T. Thackeray, Gerd Heusch, Gemma Vilahur

{"title":"Immunometabolism in heart failure","authors":"Ioanna Andreadou, Alessandra Ghigo, Panagiota-Efstathia Nikolaou, Filip K. Swirski, James T. Thackeray, Gerd Heusch, Gemma Vilahur","doi":"10.1038/s41569-025-01165-8","DOIUrl":"https://doi.org/10.1038/s41569-025-01165-8","url":null,"abstract":"The interaction between inflammation and metabolism (immunometabolism) is a crucial factor in the pathophysiology of heart failure, whether the cardiac failure originates from ischaemic injury or systemic metabolic disorders, and whether it is associated with reduced or preserved ejection fraction. Ischaemia, metabolic stress and comorbidity-driven systemic inflammation attract innate and adaptive immune cells to the myocardium and induce their polarization towards pro-inflammatory or anti-inflammatory phenotypes through cell-intrinsic metabolic shifts involving oxidative phosphorylation and anaerobic glycolysis. These infiltrating immune cells modulate cardiac and systemic metabolism. The bidirectional metabolic crosstalk between immune cells and parenchymal and stromal cardiac cells contributes to adverse cardiac remodelling. In turn, ischaemic injury and deregulated metabolism stimulate bone marrow and extramedullary myelopoiesis, which increases immune cell recruitment and perpetuates a non-resolving chronic inflammatory state. Pharmacological interventions targeting metabolism have shown promise for improving outcomes in patients with heart failure, but immunomodulatory approaches face multiple challenges. Understanding the complex metabolic pathways and cell–cell interactions that regulate immunometabolism in heart failure is essential to identify new therapies that shift the balance from maladaptive to cardioprotective immune responses. In this Review, we provide a comprehensive overview of the intricate cellular and molecular mechanisms that govern immunometabolism in heart failure and discuss potential approaches to non-invasively monitor and treat patients with heart failure.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"17 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337525","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}

引用次数: 0

Vascular (dys)function in the failing heart. 衰竭心脏的血管功能。

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-22 DOI: 10.1038/s41569-025-01163-w

Luca Liberale,Dirk Jan Duncker,Derek John Hausenloy,Simon Kraler,Hans Erik Bøtker,Bruno Karl Podesser,Gerd Heusch,Petra Kleinbongard

{"title":"Vascular (dys)function in the failing heart.","authors":"Luca Liberale,Dirk Jan Duncker,Derek John Hausenloy,Simon Kraler,Hans Erik Bøtker,Bruno Karl Podesser,Gerd Heusch,Petra Kleinbongard","doi":"10.1038/s41569-025-01163-w","DOIUrl":"https://doi.org/10.1038/s41569-025-01163-w","url":null,"abstract":"Heart failure (HF) is not confined to contractile failure of cardiomyocytes or myocardial fibrosis. Coronary and systemic vascular dysfunction contributes to the initiation and progression of HF with or without reduced ejection fraction. Furthermore, HF compromises vascular function, creating and sustaining a vicious cycle with deranging effects on coronary blood flow, cardiac metabolism and cardiac function. In HF, systemic arterial dysfunction, characterized by increased arterial stiffness and resistance, raises cardiac afterload and impedes myocardial contractile function. Reduced coronary blood flow impairs myocardial oxygen delivery and consequently cardiomyocyte metabolism and function. Coronary microvascular dysfunction is heterogeneous in its pathogenesis and manifestations, complicating the diagnosis and management across different HF phenotypes. Understanding the alterations in function in different segments of the vasculature, from the aorta to the capillary level, offers mechanistic insights into disease drivers and therapeutic interventions. Interventional approaches can improve vascular haemodynamics, whereas established and emerging pharmacotherapies target the neurohumoral axis and reduce extravascular compression, inflammation, and oxidative stress, thereby improving vascular function and HF-related outcomes. In this Review, we provide a mechanistic framework of vascular dysfunction in the pathogenesis of HF with or without reduced ejection fraction, pointing towards integrated therapies that consider the vascular implications of contemporary HF management across HF phenotypes.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"20 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337490","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}

引用次数: 0

Atheroprotection mediated by hepatic PPARα is linked to its anti-inflammatory, but not lipid-lowering, properties 肝PPARα介导的动脉粥样硬化保护与其抗炎而非降脂特性有关

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-12 DOI: 10.1038/s41569-025-01182-7

Karina Huynh

引用次数: 0

Leadless and extravascular cardiac resynchronization therapy: the future for CRT? 无铅和血管外心脏再同步化治疗：CRT的未来？

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-06 DOI: 10.1038/s41569-025-01178-3

Steven Niederer, Henry Chubb, Kenneth C. Bilchick, Christopher Aldo Rinaldi

引用次数: 0

Cardiovascular involvement in glycogen storage diseases 糖原储存病与心血管的关系

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-05 DOI: 10.1038/s41569-025-01171-w

Tomàs Pinós, Richard M. Cubbon, Alfredo Santalla, Carmen Fiuza-Luces, Alejandro Santos-Lozano, Miguel A. Martín, Joaquín Arenas, Joachim Nielsen, Niels Ørtenblad, Alejandro Lucia

{"title":"Cardiovascular involvement in glycogen storage diseases","authors":"Tomàs Pinós, Richard M. Cubbon, Alfredo Santalla, Carmen Fiuza-Luces, Alejandro Santos-Lozano, Miguel A. Martín, Joaquín Arenas, Joachim Nielsen, Niels Ørtenblad, Alejandro Lucia","doi":"10.1038/s41569-025-01171-w","DOIUrl":"https://doi.org/10.1038/s41569-025-01171-w","url":null,"abstract":"Glycogen storage diseases are rare conditions affecting both sexes that are caused by inherited deficiencies of enzymes involved either in glycogen synthesis or breakdown, or in glycolysis. The liver and skeletal muscle are usually the most affected tissues. However, because glycogen has an important role in cardiac development and function, several glycogen storage diseases are associated, at least indirectly, with cardiac disorders, some of which have severe consequences from the first months of life. Early identification of these conditions is, therefore, an important issue, and implementation of strategies to prevent fatal outcomes due to cardiovascular disease is vital. In this Review, we discuss the pathophysiological mechanisms and the preclinical, clinical and epidemiological evidence for cardiovascular involvement in various glycogen storage diseases. We also describe interventions that can help preserve heart function, including changes in nutrition and exercise, as well as the few available molecular therapies to address the underlying metabolic anomalies.","PeriodicalId":18976,"journal":{"name":"Nature Reviews Cardiology","volume":"17 1","pages":""},"PeriodicalIF":49.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218799","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}

引用次数: 0

Think Aorta: aortic dissection awareness and perspectives from the patient 思考主动脉：患者对主动脉夹层的认识和观点

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-06-03 DOI: 10.1038/s41569-025-01177-4

Gareth Owens

引用次数: 0

Networking effectively with cardiovascular societies: strategies for meaningful engagement and career advancement 有效地与心血管协会建立联系：有意义的参与和职业发展的策略

IF 49.6 1区医学

Nature Reviews Cardiology Pub Date : 2025-05-29 DOI: 10.1038/s41569-025-01174-7

Purvi Parwani, F. Aaysha Cader

引用次数: 0