Haematometabolism rewiring in atherosclerotic cardiovascular disease

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.