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  • Review Article
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Haematometabolism rewiring in atherosclerotic cardiovascular disease

Nature Reviews Cardiology volume 22, pages 414–430 (2025)Cite this article

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Abstract

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.

Key points

  • Haematometabolism dysregulation (the metabolic imbalance of haematopoiesis and efferocytosis) is an integral part of inflammation, which drives residual risk in atherosclerotic cardiovascular disease.

  • Nature-related (for example, ageing and clonal haematopoiesis of indeterminate potential) and nurture-related (such as an unhealthy lifestyle) risk factors for atherosclerosis influence haematometabolism by creating an imbalance between erythropoiesis/megakaryopoiesis and myelopoiesis.

  • The energy imbalance linked to a chronic inflammatory state alters the homeostasis of different blood cell lineages, propagating a quantitative and qualitative drift in the leukocyte supply chain.

  • Improving our understanding of the influence of lifestyle changes on haematometabolism could contribute to the diagnosis, prognosis and treatment of atherosclerosis.

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Fig. 1: Haematometabolic control of stem cell homeostasis, CHIP and atherosclerosis.
Fig. 2: Haematometabolic control of erythropoiesis and megakaryopoiesis: the oxygen–iron–haem triad in atherosclerosis.
Fig. 3: Haematometabolic control of myelopoiesis: the cholesterol–glycolysis interplay in atherosclerosis.

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Acknowledgements

L.Y.C. received grants from the European Research Council (ERC) consolidator programme (ERC2016COG724838), Agence Nationale de la Recherche (ANR) (Glutadiab19-CE17-0030-DS; CHIC 20-CE14-009; MacBurn 21-CE14-0023; Glutacare 24-CE14-7125), IHU RespirERA (Respiratory Health, Environment and Ageing) and Fondation de France (FDF).

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  1. Institut National de la Santé et de la Recherche Médicale (Inserm) U1065, Nice, France

    Laurent Yvan-Charvet, Thibault Barouillet & Coraline Borowczyk

  2. Université Côte d’Azur, Centre Méditerranéen de Médecine Moléculaire (C3M), Nice, France

    Laurent Yvan-Charvet, Thibault Barouillet & Coraline Borowczyk

  3. Fédération Hospitalo-Universitaire (FHU) Oncoage, IHU ResprERA Respiratory Health, Environment and Ageing (RespirERA), Nice, France

    Laurent Yvan-Charvet, Thibault Barouillet & Coraline Borowczyk

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Yvan-Charvet, L., Barouillet, T. & Borowczyk, C. Haematometabolism rewiring in atherosclerotic cardiovascular disease. Nat Rev Cardiol 22, 414–430 (2025). https://doi.org/10.1038/s41569-024-01108-9

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