Trafficking of Mononuclear Phagocytes in Healthy Arteries and Atherosclerosis

Abstract

Monocytes and macrophages play essential roles in all stages of atherosclerosis – from early precursor lesions to advanced stages of the disease. Intima-resident macrophages are among the first cells to be confronted with the influx and retention of apolipoprotein B-containing lipoproteins at the onset of hypercholesterolemia and atherosclerosis development. In this review, we outline the trafficking of monocytes and macrophages in and out of the healthy aorta, as well as the adaptation of their migratory behaviour during hypercholesterolemia. Furthermore, we discuss the functional and ontogenetic composition of the aortic pool of mononuclear phagocytes and its link to the atherosclerotic disease process. The development of mouse models of atherosclerosis regression in recent years, has enabled scientists to investigate the behaviour of monocytes and macrophages during the resolution of atherosclerosis. Herein, we describe the dynamics of these mononuclear phagocytes upon cessation of hypercholesterolemia and how they contribute to the restoration of tissue homeostasis. The aim of this review is to provide an insight into the trafficking, fate and disease-relevant dynamics of monocytes and macrophages during atherosclerosis, and to highlight remaining questions. We focus on the results of rodent studies, as analysis of cellular fates requires experimental manipulations that cannot be performed in humans but point out findings that could be replicated in human tissues. Understanding of the biology of macrophages in atherosclerosis provides an important basis for the development of therapeutic strategies to limit lesion formation and promote plaque regression.

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

“…An essential stage in the inflammatory process involves the penetration of monocytes into the subendothelial region of major arteries and their subsequent transformation into tissue macrophages. The activation and functioning of these macrophages are regulated by the cytokines present in the inflammatory environment of the atherosclerotic lesion [194]. MASLD exhibits a strong correlation with AS and appears to serve as an early risk factor for the development of AS [195].…”

Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

“…359 Cytokines released by mononuclear cells stimulate the proliferation of smooth muscle cells in the media of blood vessels and the new intima. 360 In addition, mononuclear cells activate into macrophages, during which smooth muscle cells of the new intima ingest lipids to become foam cells, forming atheromatous plaques. 361,362 Atherogenesis is related to hypoxia.…”

Identification of Monocyte-Associated Genes Related to the Instability of Atherosclerosis Plaque

“…Also, the underlying mechanism of macrophages and foam cells involved in atherosclerotic plaque instability and rupture has been partially characterized [15,16]. Numerous studies have reported that monocytes play an essential role in atherosclerotic, but monocyteassociated genes' effect on plaque instability is still not very clear [17][18][19][20][21]. Therefore, it is essential to explore the clinical significance and potential mechanisms of monocyte-associated genes in atherosclerotic plaque instability through the combined single-cell sequencing and transcriptomics data analysis.…”