LDL-C and Lp(a) push monocytes and macrophages into a self-perpetuating foam-cell-forming, pro-inflammatory cycle, review explains (Biochem Med (Zagreb) 2025)

Atherosclerosis is an active interaction between lipoproteins and inflammatory cells. Monocytes and macrophages are the most important immune cells involved in the process of atherosclerosis. They interact with atherogenic lipoproteins, in particular low density lipoprotein (LDL) cholesterol and lipoprotein(a) (Lp(a)). The increased concentration of the LDL cholesterol and Lp(a) accelerates the polarization of monocytes and macrophages toward proinflammatory phenotype and the formation of the foam cells. These cells then release large quantities of inflammatory cytokines that stimulate the oxidation of atherogenic lipoproteins that are even more atherogenic and contribute to the formation of foam cells and the secretion of the pro-inflammatory cytokines, thus creating a vicious circle. Surface marker C-C chemokine receptor type 2, expressed on monocytes/macrophages, enables their adhesion and migration into the subendothelial layer. The rupture of the atherosclerotic plaque on one hand, and the ability of the oxidized LDL cholesterol and Lp(a) to trigger arterial thrombosis by different mechanisms on the other hand, result in acute cardiovascular event. Here, we summarize the role of the monocytes and macrophages in atherosclerosis and explore the influence of LDL cholesterol and Lp(a) on monocytes and macrophages during the entire process of atherosclerosis, from its initiation to progression.