Abstract
Atherosclerosis is a multifactorial chronic disease that has a prominent inflammatory component. Currently, atherosclerosis is regarded as an active autoimmune process that involves both innate and adaptive immune pathways. One of the drivers of this process is the presence of modified low-density lipoprotein (LDL). For instance, lipoprotein oxidation leads to the formation of oxidation-specific epitopes (OSE) that can be recognized by the immune cells. Macrophage response to OSEs is recognized as a key trigger for initiation and a stimulator of progression of the inflammatory process in the arteries. At the same time, the role of oxidized LDL components is not limited to pro-inflammatory stimulation, but includes immunoregulatory effects that can have protective functions. It is, therefore, important to better understand the complexity of oxidized LDL effects in atherosclerosis in order to develop new therapeutic approaches to correct the inflammatory and metabolic imbalance associated with this disorder. In this review, we discuss the process of oxidized LDL formation, mechanisms of OSE recognition by macrophages and the role of these processes in atherosclerosis.
Highlights
Published: 29 July 2021The multifactorial nature of atherosclerosis pathogenesis makes studying this disease challenging
In a model of minimally oxidized low-density lipoprotein (LDL) in which native LDL is modified by cells expressing 12/15-lipoxygenase, macrophage activation was associated with oxidized cholesteryl esters (CE)
Oxidized lipids and lipoproteins act as damage-associated molecular patterns (DAMPs) and are sensed by a number of pattern recognition receptors
Summary
The multifactorial nature of atherosclerosis pathogenesis makes studying this disease challenging. OxLDL provides for oxidation-specific epitopes (OSE) that can be recognized by the innate immune system cells as damage-associated molecular patterns (DAMPs) [9]. Following oxLDL recognition and internalization, macrophages undergo metabolic and functional reprogramming [11] This process involves decrease of phagocytic activity, increase of pro-inflammatory cytokines production, and differentiation of macrophages into foam cells. Possible anti-inflammatory signaling properties of oxLDL should not be neglected, since they may be important for tissue reparation and inflammation resolution It this work, we discuss both aspects of oxLDL interaction with immune cells and the role of such interactions in atherosclerosis
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