Immunology articles within Nature Reviews Cardiology

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  • Review Article |

    In this Review, van Leent and colleagues provide an overview of current PET imaging approaches for assessment of atherosclerotic cardiovascular disease, as well as of whole-body PET applications; discuss the link between imaging readouts and atherosclerotic plaque pathology; and highlight promising developments in PET systems and radiotracer synthesis.

    • Alexander Maier
    • , Abraham J. P. Teunissen
    •  & Mandy M. T. van Leent

  • Journal Club |

    Shoaran and Maffia recount how our understanding of the role of inflammation in atherosclerosis has evolved and highlight the study by Göran Hansson and colleagues that provided the first hint of the involvement of the adaptive immune response in atherosclerosis.

    • Mohsen Shoaran
    •  & Pasquale Maffia

  • Review Article |

    In this Review, Fredman and Serhan discuss the role of specialized pro-resolving mediators, a superfamily of endogenous signalling lipids that mediate resolution of inflammation processes in atherosclerosis, and appraise the therapeutic potential of specialized pro-resolving mediators for the prevention and treatment of atherosclerosis, and the resolution of uncontrolled vascular inflammation.

    • Gabrielle Fredman
    •  & Charles N. Serhan

  • Review Article |

    In this Review, Guzik and colleagues discuss immune and inflammatory mechanisms of hypertension, including upstream regulators and downstream effectors as well as the complex interplay between the immune system, blood pressure regulation and end-organ damage, which can help to identify new targets for therapeutic interventions.

    • Tomasz J. Guzik
    • , Ryszard Nosalski
    •  & Grant R. Drummond

  • Review Article |

    The NLRP3 inflammasome can sense cardiac ischaemic and non-ischaemic injury, amplify the inflammatory response and induce inflammatory cell death. In this Review, Toldo and Abbate describe the role of the NLRP3 inflammasome in numerous cardiac pathologies and summarize evidence on the use of agents targeting the NLRP3 inflammasome and related cytokines.

    • Stefano Toldo
    •  & Antonio Abbate

  • Research Highlight |

    SARS-CoV-2 infects macrophages, especially lipid-laden foam cells, in coronary atherosclerotic plaques in patients with COVID-19; this infection initiates a strong proatherogenic inflammatory response, which might contribute to the ischaemic cardiovascular complications in these patients.

    • Gregory B. Lim

  • Review Article |

    In this Review, Swirski and co-workers discuss how lifestyle factors modulate haematopoiesis and leukocyte migration in the context of cardiovascular homeostasis and disease, with particular focus on the role of the nervous system as the key executor connecting environmental influences to leukocyte behaviour.

    • Henrike Janssen
    • , Laura L. Koekkoek
    •  & Filip K. Swirski

  • Review Article |

    In this Review, the authors discuss the clinical and experimental data on immunomodulatory effects of evidence-based treatments for heart failure and their primary mechanisms of action, and highlight potential therapeutic targets and opportunities for the development and application of novel immunomodulatory treatments for heart failure.

    • George Markousis-Mavrogenis
    • , Lukas Baumhove
    •  & Peter van der Meer

  • Review Article |

    In this Review, Riksen and colleagues discuss the molecular and cellular mechanisms of trained immunity, the activation of these mechanisms by cardiovascular risk factors, and how trained immunity might contribute to atherosclerosis and atherosclerotic cardiovascular disease. The authors also propose potential strategies for the therapeutic modulation of trained immunity in atherosclerotic cardiovascular disease.

    • Niels P. Riksen
    • , Siroon Bekkering
    •  & Mihai G. Netea

  • Clinical Outlook |

    Contemporary tools to predict cardiovascular risk lack accuracy on an individual-patient level. The use of single-cell RNA sequencing to identify specific leukocyte patterns might overcome some of these limitations, propelling us towards a precision medicine approach.

    • Johannes Gollmer
    •  & Andreas Zirlik

  • Comment |

    Clonal haematopoiesis of indeterminate potential (CHIP) is defined as an expansion of mutant blood stem cells in individuals without haematological malignancies. CHIP is linked to an increased risk of non-cancerous disorders such as atherosclerotic cardiovascular disease, possibly because mutant innate immune cells have pro-inflammatory phenotypes. Prospective studies are needed to determine whether individuals with CHIP might benefit from anti-inflammatory therapies.

    • Herra Ahmad
    •  & Siddhartha Jaiswal

  • Comment |

    IgM antibodies have gained much attention as risk markers of atherosclerotic cardiovascular disease, but the exact antigenic determinants and the full spectrum of functions remain to be defined. A better understanding of the potentially diverse nature of the antigens that they recognize will help to dissect the function of IgM in atherosclerosis.

    • Justine Deroissart
    •  & Christoph J. Binder

  • Comment |

    Excessive salt intake is a known risk factor for cardiovascular disease commonly associated with hypertension. However, we propose that a high-salt diet can promote cardiovascular and other diseases independently of high blood pressure through inflammatory pathways that increase the production of myeloid cells.

    • Man K. S. Lee
    •  & Andrew J. Murphy

  • Research Highlight |

    A subpopulation of cardiac-resident macrophages protect the heart against sepsis-induced cardiomyopathy by scavenging dysfunctional mitochondria ejected from cardiomyocytes; modulation or administration of these macrophages might be a potential therapeutic strategy.

    • Gregory B. Lim

  • Review Article |

    Macrophages are one of the most active cell types during all stages after myocardial infarction. In this Review, Boisvert and co-workers describe the populations of cardiac macrophage involved in myocardial infarction, their cardioprotective functions and their interactions with other cardiac cell types. The authors also explore potential therapeutic approaches to target macrophage-mediated inflammation in myocardial infarction.

    • Jonathan Yap
    • , Jason Irei
    •  & William A. Boisvert

  • Clinical Outlook |

    Immune checkpoint inhibitors (ICIs) have become a pillar of cancer therapy. The cardiovascular complications of ICIs extend beyond myocarditis and can involve any component of the cardiovascular system, including the pericardium, coronary arteries and conduction system. Clinicians caring for patients treated with ICIs must be vigilant for the cardiovascular complications of these therapies, which might portend a poor prognosis.

    • Kiranbir Josan
    •  & Tomas G. Neilan

  • Comment |

    Important lessons about human susceptibility to coronary atherosclerosis can be learned from the relative resilience of chimpanzees to coronary artery disease (CAD), despite their higher baseline plasma levels of LDL cholesterol and lipoprotein(a) than in humans. Evolutionary pressure and hyper-reactive T cells might have a role in the unique susceptibility of humans to CAD.

    • Gemma A. Figtree
    • , Jason C. Kovacic
    •  & Helen M. McGuire

  • Review Article |

    In this Review, the authors summarize the latest advances in cardioimmunology and discuss experimental tools and strategies that are currently available for the study of immune cells, guiding readers through case-based examples to provide recommendations for the use of immunological tools and strategies in the study of immune cells in cardiac disease.

    • Anthony Wong
    • , Homaira Hamidzada
    •  & Slava Epelman

  • Research Highlight |

    Statins increase the rate of macrophage efferocytosis through suppression of the expression of the ‘don’t-eat-me’ molecule CD47 on atherosclerotic plaque apoptotic cells, and pro-efferocytic therapies amplify the anti-atherosclerotic effects of statin treatment in an additive manner and independently of any lipid-lowering effects of statins.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, the authors provide an overview of the immune cells involved in atherosclerosis, discuss preclinical research and published and ongoing clinical trials assessing the therapeutic potential of targeting the immune system in atherosclerosis, highlight emerging therapeutic targets from preclinical studies and identify challenges for successful clinical translation.

    • Suzanne E. Engelen
    • , Alice J. B. Robinson
    •  & Claudia Monaco

  • Comment |

    The risk of acute myocarditis associated with COVID-19 mRNA vaccination has garnered intense (social) media attention. However, myocarditis after COVID-19 mRNA vaccination is rare and usually resolves within days or weeks. Moreover, the risks of hospitalization and death associated with COVID-19 are greater than the risk associated with COVID-19 vaccination. Therefore, COVID-19 vaccination should be recommended in adolescents and adults.

    • Stephane Heymans
    •  & Leslie T. Cooper

  • Research Highlight |

    A new study shows that anti-IL-1β treatment and NLRP3 inflammasome inhibition ameliorate vascular inflammation and atherosclerosis progression by two mechanisms: a reduction in blood inflammatory leukocyte supply and a decrease in inflammatory leukocyte uptake into atherosclerotic lesions.

    • Irene Fernández-Ruiz

  • Research Highlight |

    A new study now shows that basophils can influence cardiac remodelling after myocardial infarction. Despite their low number in the injured myocardium, basophils strongly affected other immune cells involved in cardiac repair and remodelling in mice, promoting cardiac healing by facilitating the polarization of reparative macrophages.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, Fernandez and Giannarelli discuss how single-cell technologies can advance our understanding of the cellular and molecular composition of atherosclerotic plaques and how these approaches can guide the design of new, personalized immunotherapies and immune monitoring tools for the management of patients with atherosclerotic cardiovascular disease.

    • Dawn M. Fernandez
    •  & Chiara Giannarelli

  • News & Views |

    Nanotherapies are emerging rapidly as options to treat cardiovascular disease. However, insufficient and heterogeneous delivery remain critical issues. Novel strategies to boost targeted delivery of systemically administered nanoparticles by optimizing the particle physical properties or using immune cells as carriers promise to increase nanotherapeutic effectiveness in cardiovascular and other inflammatory diseases.

    • Bryan Ronain Smith

  • Review Article |

    Fatty acids affect the pathogenesis of atherosclerosis, and accumulating evidence shows that fatty acids also modulate T cell functions and processes. This Review summarizes the effects of circulating fatty acids on the metabolism, activation, proliferation and polarization of T cells and how these changes influence the subsequent functions of T cells in the pathogenesis of atherosclerosis.

    • Nathalie A. Reilly
    • , Esther Lutgens
    •  & J. Wouter Jukema

  • Research Highlight |

    The CD200 inhibitory immune checkpoint promotes arterial homeostasis and reduces atherosclerotic plaque progression and inflammation in mice by limiting the excessive supply, recruitment and activation of monocytes and macrophages during atherogenesis, according to a new study.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, Stark and Massberg discuss how the interplay between innate immunity, platelet activation and coagulation, known as immunothrombosis, functions as a host defence mechanism to limit pathogen spreading, yet its aberrant activation, termed thromboinflammation, results in thrombotic complications, highlighting the therapeutic potential of anti-inflammatory strategies in cardiovascular pathologies.

    • Konstantin Stark
    •  & Steffen Massberg

  • Research Highlight |

    In ischaemic tissues, macrophages accumulate in the perivascular region and regulate blood flow by releasing nitric oxide derived from inducible nitric oxide synthase, thereby increasing muscle perfusion and improving limb function.

    • Gregory B. Lim

  • Review Article |

    In this Review, Nahrendorf and colleagues discuss the electrophysiological properties of leukocytes and how these cells relate to conduction in the heart, aiming to bridge the knowledge gap between electrophysiology and immunology and to explore the roles of leukocytes in cardiac conduction and arrhythmia.

    • Jana Grune
    • , Masahiro Yamazoe
    •  & Matthias Nahrendorf

  • Research Highlight |

    Alarmins released by infarcted myocardium stimulate B cells to differentiate into antibody-producing plasma cells, which then remotely drive the progression of atherosclerosis by producing autoantibodies that accumulate in pre-existing atherosclerotic plaques, increasing local inflammation and accelerating the progression towards a vulnerable plaque phenotype.

    • Irene Fernández-Ruiz

  • Review Article |

    This Review summarizes the latest evidence indicating that platelet and endothelial dysfunction are essential components of COVID-19 pathology, describes the potential mechanisms underlying the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19, and highlights the roles of coagulopathy, thrombocytopathy and endotheliopathy in COVID-19 pathogenesis.

    • Sean X. Gu
    • , Tarun Tyagi
    •  & John Hwa

  • Research Highlight |

    A network of macrophages in the heart supports cardiac health and function by removing dysfunctional mitochondria and waste material released from cardiomyocytes in subcellular particles called exophers.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, Tyrrell and Goldstein discuss vascular intrinsic and extrinsic mechanisms of how ageing promotes atherosclerosis, including changes in myeloid cells, mitochondrial dysfunction, impaired mitophagy and elevated IL-6 levels. They propose future steps for research and potential therapeutic approaches for age-related atherosclerosis.

    • Daniel J. Tyrrell
    •  & Daniel R. Goldstein

  • Research Highlight |

    A new study shows that regulatory T cells have essential roles in atherosclerotic plaque regression by promoting the resolution of plaque inflammation through suppression of macrophage and T cell pro-inflammatory responses and induction of a pro-resolving macrophage phenotype.

    • Irene Fernández-Ruiz

  • Review Article |

    In this Review, Soehnlein and colleagues discuss the role of neutrophils in cardiovascular inflammation and repair, describing the effect of cardiovascular risk factors on neutrophil production and function, appraising the contribution of neutrophils to the different stages of atherosclerosis and its clinical manifestations, and highlighting the evolving therapeutic strategies for targeting neutrophil numbers, functional status and effector mechanisms.

    • Carlos Silvestre-Roig
    • , Quinte Braster
    •  & Oliver Soehnlein

  • Review Article |

    Inflammation has an important role in the pathogenesis of acute and chronic heart failure. This Review summarizes the latest findings on the role of the innate and adaptive immune systems in the pathogenesis of heart failure, and highlights the results of phase III clinical trials of therapies targeting inflammatory processes in this condition, such as anti-inflammatory and immunomodulatory strategies.

    • Luigi Adamo
    • , Cibele Rocha-Resende
    •  & Douglas L. Mann

  • Review Article |

    This Review summarizes the role of transcription factors and epigenetic remodelling in modulating macrophage plasticity, provides an overview of the cooperative action of transcription factors and epigenetic modifiers controlling macrophage activation in the context of atherosclerosis and inflammation, and highlights the therapeutic potential of modulating transcription factor activity.

    • Tatyana Kuznetsova
    • , Koen H. M. Prange
    •  & Menno P. J. de Winther

  • Research Highlight |

    A new study shows that clonal haematopoiesis of indeterminate potential (CHIP)-driver mutations in DNMT3A or TET2 are associated with increased medium-term mortality in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

    • Gregory B. Lim

  • Research Highlight |

    Neutrophils exacerbate tissue damage and inflammation in advanced atherosclerosis by triggering smooth muscle cell (SMC) lysis and death. Lesional neutrophils release neutrophil extracellular traps that contain histone H4, which interacts with SMCs to induce cell lysis, leading to the destabilization of atherosclerotic plaques.

    • Irene Fernández-Ruiz

  • Review Article |

    Atherosclerosis is characterized by low-grade, chronic inflammation, and the balance between pro-inflammatory and inflammation-resolving mechanisms dictates the clinical outcomes. This Review discusses the specific causes of inflammation and the mechanisms underlying the impaired resolution of inflammation that characterize clinically dangerous atherosclerotic lesions and highlights the potential of pro-resolving mediator therapy for the prevention and treatment of atherosclerotic cardiovascular disease.

    • Magnus Bäck
    • , Arif Yurdagul Jr
    •  & Petri T. Kovanen

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