Immune system and cardiovascular disease

Regulatory T (T_REG) cells are important for the induction and maintenance of immune homeostasis and tolerance. Numerous experimental and clinical studies have suggested a role for T_REG cells in protection against cardiovascular diseases, particularly atherosclerosis and abdominal aortic aneurysms. In this Review, Meng and colleagues summarize the available evidence on the role of T_REGcells in several cardiovascular disorders, such as atherosclerosis, hypertension, Kawasaki disease, and myocardial infarction.

Mast cells have many roles in the pathogenesis of cardiometabolic diseases. In this Review, Shi et al. explore the mechanistic role of mast cells in atherogenesis and its atherothrombotic complications, as well as in aortic aneurysm, valvular disease, obesity, and diabetes mellitus. Pharmacological inhibition of mast-cell activation or their targeted effector functions offers potential novel therapeutic strategies for patients with cardiometabolic disorders.

An increasing body of evidence suggests that proteins involved in the inflammatory response are also involved in the pathophysiology of atrial fibrillation (AF). Moreover, AF itself can induce inflammation. In this Review, Hu and colleagues discuss the interplay between inflammation and AF. The authors also highlight potential therapies that might be used to treat inflammation-induced AF.

Atherosclerosis is a chronic inflammatory disease of the arterial wall with multiple immune mediators implicated in its pathogenesis. Despite the wide range of anti-inflammatory drugs already in use to treat immune disorders, studies to determine whether anti-inflammatory therapies can improve cardiovascular outcomes are necessary before these treatments become a part of cardiovascular prevention. In this Review, Bäck and Hansson describe existing therapies in use for inflammatory diseases and explore the therapeutic potential of targeting immune activation in patients with atherosclerosis.

Atherosclerosis is characterized by increased accumulation of macrophages within the vessel wall. In response to stimuli such as modified lipids, cytokines, and senescent erythrocytes present in the atherosclerotic lesion, these macrophages can alter their functional phenotypes. Different macrophage subsets can influence the growth and composition of the atherosclerotic plaque in distinct ways. In this Review, Chinetti-Gbaguidi et al. highlight the diverse range of macrophage phenotypes present in atherosclerotic lesions, and their roles in both plaque progression and stability.

Myocardial infarction initiates an inflammatory response that is required for repair of, but also contributes to, heart failure. In this Review, Nikolaos Frangogiannis, outlines our current understanding of the inflammatory response in the infarcted heart, and highlights potential therapies that might counterbalance the destructive effects of this immune response.

The accumulation of lipid-laden macrophages in atherosclerotic lesions occurs preferentially at branching sites owing to poor adaptation of endothelial cells to disturbed blood flow. MicroRNAs (miRNAs) have been implicated in the pathogenic mechanisms of unresolved inflammation that precede and potentiate atherosclerosis. In this Review, Schober and colleagues provide an overview of the role of miRNAs in homeostasis and dysfunction of endothelial cells and macrophages in atherosclerosis, and explore the potential of novel miRNA-based diagnostics and therapeutic strategies.

¹⁸F-FDG is the most-commonly used tracer in PET imaging of atherosclerosis.¹⁸F-FDG uptake can be used to identify patients at the highest risk of clinical events and as a surrogate end point in clinical trials of antiatherosclerotic therapies. However, background myocardial uptake of ¹⁸F-FDG can make identifying high-risk coronary artery plaque difficult. Several novel PET tracers have, therefore, also been tested in atherosclerosis imaging. Here, Tarkin et al. review the role of state-of-the-art PET imaging of inflammation in atherosclerosis, including the rationale for this modality, and its current and future uses.

This Review explores the pathophysiology and natural history of viral myocarditis—a common cause of dilated cardiomyopathy and sudden cardiac death. Despite established standards, heterogeneity exists in the evaluation, diagnosis, and treatment of patients with myocarditis, and these aspects are also covered in detail by Pollack and colleagues. Investigational treatment options are highlighted.

Many patients with pericarditis experience recurrent episodes. In this Review, Imazio et al. emphasize the importance of identifying the aetiology of the disease, and summarize the available evidence for the various treatment options. First-line anti-inflammatory therapy involves aspirin, NSAIDs, and colchicine; additional and alternative options include corticosteroids, anakinra, azathioprine, and intravenous immunoglobulins.

A new report has demonstrated the combined use of optical coherence tomography and molecular imaging within human coronary arteries. This combination provides a unique opportunity to look at plaque from a view not previously possible, opening the field for greater understanding of plaque biology in research and clinical practice.

This Review describes the immune responses that occur in the heart, explaining how different innate and adaptive immune cell populations can have beneficial or detrimental roles during cardiac tissue injury. In particular, the authors focus on the unique macrophage subsets that are found in the heart and their roles in regenerating damaged cardiac tissue.

The accumulation of cholesterol in macrophages and other immune cells promotes inflammatory responses. Inflammation, in turn, reduces the normal physiological excretion of cholesterol, which amplifies the inflammatory response and promotes myelopoiesis. Here, the authors detail the mechanisms by which cholesterol accumulation affects immune signalling pathways and highlight potential therapeutic interventions that may have benefits for metabolic diseases.

Cardiovascular disease and rheumatoid arthritis (RA) share genetic and environmental risk factors, as well as pathological processes. This article outlines the mechanisms that might contribute to the prevalence and characteristic phenotype of atherosclerosis in RA, with an emphasis on inflammation.

Reciprocal interactions between leukocytes and endothelial cells enable leukocytes to recognize the blood vessel endothelium in areas of inflammation and transmigrate across the endothelial barrier to mount an immune response in infected and/or damaged tissues.

In this Review, the authors provide a comprehensive overview of the role of macrophage dynamics in determining the initiation, progression and regression of atherosclerotic inflammation. Understanding the factors that determine the inflammatory state of the plaque may help to identify potential therapeutic targets for plaque regression.