Macrophages and Foam Cells: Brief Overview of Their Role, Linkage, and Targeting Potential in Atherosclerosis

Abstract

Atherosclerosis is still one of the main causes of death around the globe. This condition leads to various life-threatening cardiovascular complications. However, no effective preventive measures are known apart from lifestyle corrections, and no cure has been developed. Despite numerous studies in the field of atherogenesis, there are still huge gaps in already poor understanding of mechanisms that underlie the disease. Inflammation and lipid metabolism violations are undoubtedly the key players, but many other factors, such as oxidative stress, endothelial dysfunction, contribute to the pathogenesis of atherosclerosis. This overview is focusing on the role of macrophages in atherogenesis, which are at the same time a part of the inflammatory response, and also tightly linked to the foam cell formation, thus taking part in both crucial for atherogenesis processes. Being essentially involved in atherosclerosis development, macrophages and foam cells have attracted attention as a promising target for therapeutic approaches.

Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms

“…Foam cell formation is a key step in the initiation and progression of atherosclerosis ( 6 ). Lipid homeostasis is maintained by the proper function of lipid uptake, efflux, and esterification.…”

Lipid Droplets, Phospholipase A2, Arachidonic Acid, and Atherosclerosis

“…Recent work has shown that a constant flux of monocytes from the bloodstream into the intima appears to be necessary for the atheromatous plaque to effectively progress [ 68 ]. Interest in the heterogeneity of macrophages in atherosclerotic lesions, in particular with regard to the macrophages involved in a proinflammatory process versus those participating in resolution and repair events, has prompted a large number of recent studies [ 69 , 70 ]. However, the results are yet inconclusive because in vitro studies do not adequately reproduce the situation existing in the atherosclerotic endothelium.…”

“…The fact that circulating monocytes are attracted to damaged areas of the endothelium and, once inside the intima, turn into foamy macrophages, is a concept that has been firmly established for decades [ 61 , 69 , 70 ]. Nevertheless, another model has emerged according to which monocytes interacting with products released by endothelial cells may acquire a foamy phenotype long before crossing the arterial endothelial barrier and differentiating into foamy macrophages in the intima [ 71 , 72 , 73 , 74 , 75 ] ( Figure 2 ).…”

Epigenetic Regulation in Pathology of Atherosclerosis: A Novel Perspective

“…Atherosclerosis is the result of lipid metabolism disorder in the body, the disbalance of influx and efflux of lipids, especially for low-density lipoprotein (LDL) and oxidized low-density lipoprotein (Ox-LDL), gradually leads to chronic inflammation in blood vessels ( Poznyak et al, 2021 ). The pathological process of atherosclerosis involves multiple types of cells and can be seen as the chronic inflammatory process of the blood vessel wall ( Khan et al, 2021 ).…”