Series |

Mechanisms of atherosclerosis

An ongoing Series of articles from Nature Reviews Cardiology exploring the pathophysiological mechanisms of atherosclerosis and the potential for developing novel diagnostic, preventative and therapeutic interventions.

Reviews

In this Review, Mehta and Shapiro discuss the mechanisms by which apolipoproteins regulate lipoprotein metabolism and thereby influence vascular biology and atherosclerotic disease. Advances in the understanding of apolipoprotein biology and their translation into therapeutic agents to reduce the risk of cardiovascular disease are also highlighted.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

In this Review, Gotto and colleagues summarize the evolution of our understanding of HDL structure and function, current models of atheroprotection by HDL involving reverse cholesterol transport, and their identification of a correlation between the bioavailability of free cholesterol contained in HDL and atherogenesis.

Review Article | | Nature Reviews Cardiology

Atherosclerotic plaque erosion is becoming an increasingly common characteristic of culprit lesions in acute coronary syndromes. In this Review, Fahed and Jang discuss the patient phenotype and the molecular characteristics in plaque erosion and provide their vision for a potential major shift in the management of patients with plaque erosion.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

Accumulating evidence supports the critical role of T cells as drivers and modifiers of atherosclerosis. In this Review, Ley and colleagues describe the latest advances in our understanding of the role of T cell subsets in atherosclerosis, discuss the process of T cell homing to atherosclerotic plaques and highlight potential T cell-related therapies for atherosclerosis.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

Clonal haematopoiesis of indeterminate potential (CHIP) commonly occurs as a result of mutations in transcriptional regulators and is associated with a doubling of the risk of atherosclerotic cardiovascular disease. Jaiswal and Libby propose that CHIP contributes to the increased inflammation seen in ageing and thereby explains some of the age-related risk of cardiovascular disease.

Review Article | | Nature Reviews Cardiology

The shear stress generated by flowing blood has major effects on vascular function, with low shear stress promoting vascular dysfunction and atherosclerosis. This Review describes the latest findings on how endothelial cells decode complex shear stress environments to regulate physiological and pathophysiological responses, highlighting the role of pathways involved in embryonic development.

Review Article | | Nature Reviews Cardiology

In this Review, Mallat and colleagues critically evaluate the studies on the origin, fate and functions of vascular smooth muscle cells (VSMCs) in atherosclerosis, highlighting the importance of developmental origin, clonal expansion and plasticity of VSMCs cells in atherosclerosis and summarizing the roles of VSMCs and VSMC-derived cells in plaque development and progression.

Review Article | | Nature Reviews Cardiology

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.

Review Article | | Nature Reviews Cardiology

Antibody-producing B cells perform a unique role in responses to stress, injury, and infection. In this Review, Sage and colleagues discuss the spectrum of B cell involvement in dyslipidaemia and atherosclerotic plaque development.

Review Article | | Nature Reviews Cardiology

News & Comment

Atherosclerosis causes myocardial infarction, ischaemic cardiomyopathy, many ischaemic strokes and jeopardized limbs. Despite enormous progress, atherosclerosis has become the major cause of death worldwide. This Comment intertwines clinical and basic advances in atherosclerosis to illustrate their interdependence, which provides a template for a way forwards to conquer the scourge of atherosclerotic cardiovascular disease.

Comment | | Nature Reviews Cardiology

Sequencing studies demonstrate a strong clinical association between clonal haematopoiesis driven by acquired mutations and atherosclerotic disease. Previous research supports the idea that this association reflects a direct contribution of some clonal haematopoiesis-related mutations to atherosclerosis. Now, mathematical modelling suggests that atherosclerosis could instead accelerate clonal haematopoiesis.

News & Views | | Nature Reviews Cardiology

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.

Research Highlight | | Nature Reviews Cardiology