The sentinels of coronary artery disease: heterogeneous monocytes

Abstract

Monocytes are heterogeneous immune cells that play a crucial role in the inflammatory response during atherosclerosis, influencing the progression and outcome of the disease. In the pathogenesis of atherosclerotic diseases, such as coronary artery disease (CAD), monocytes not only serve as the initial sensors of endogenous and exogenous pathogenic factors, but also function as intermediators that bridge the circulatory system and localized lesions. In the bloodstream, heterogeneous monocytes, acting as sentinels, are rapidly recruited to atherosclerotic lesions, where they exhibit a heightened capacity to respond to various pathological stimuli upon detecting signals from damaged vascular endothelial cells. Clinical studies have demonstrated that the heterogeneity of monocytes in CAD patients presents both diversity and complexity, varying across different disease subtypes and pathological stages. This review explores the heterogeneity of monocytes in CAD, focusing on alterations in monocyte subset numbers, proportions, and the expression of functional receptors, as well as their correlations with clinical features. Additionally, we propose strategies to enhance the clinical utility value of monocyte heterogeneity and outline future research directions in the field of CAD. With the widespread application of high-parameter flow cytometry and single-cell sequencing technologies, it is anticipated that a comprehensive understanding of monocyte heterogeneity in CAD will be achieved, enabling the identification of disease-specific monocyte subtypes. This could offer new opportunities for improving the diagnosis and treatment of CAD.

Keywords: atherosclerosis; coronary artery disease; flow cytometry; inflammation; monocyte heterogeneity.

Figure 1

The role of circulating monocyte heterogeneity in Atherosclerosis. Mon1 is the great subtype of circulating monocytes, its main function is to respond to bacterial stimulation of phagocytosis and production of ROS. Mon1 cells were demonstrated to differentiate into Mon2, which in turn differentiated into Mon3 monocytes. In contrast to Mon1, Mon3 cells produce anti-inflammatory cytokines and proinflammatory cytokines, such as IL-10 and IFN-α, in response to bacterial and viral responses, respectively. Mon3 patrol the vascular system in a steady state to show the “patrol” function, which is helpful to maintain vascular integrity. Mon2 cells exhibit both Mon1 and Mon3 molecular phenotypes, and their functional characteristics often overlap. HSPC, hematopoietic stem progenitor cell; ROS, reactive oxygen species; LDL, low-density lipoprotein; SMC, smooth muscle cell; DC, dendritic cells.