Life cycle of macrophages in atherosclerotic inflammation progression and resolution: mediators and interventions (narrative review)

Abstract

Abstract As one of the pathological causes of coronary heart disease, atherosclerosis poses a major threat to human health. Macrophages play an important role in regulating atherosclerotic disease progression. Specifically, atherosclerotic inflammation is initiated when low-density lipoproteins infiltrate the subcutaneous area and are phagocytosed by macrophages, leading to foam cell formation. The subsequent inflammation progression or resolution depends on the delicate balance between proinflammatory and anti-inflammatory mediators. In cases where proinflammatory factors dominate, macrophages tend to activate the pyroptosis and necrosis pathways, resulting in the release of intracellular damage-associated molecular patterns and promoting necrotic core formation and plaque progression. Conversely, when anti-inflammatory factors prevail, macrophages engage in autophagy-mediated intracellular lipid metabolism while inhibiting inflammation progression through the efferocytosis of apoptotic cells. The regulatory function of macrophages in atherosclerosis can also be understood from the perspective of their life cycles. Lipid retention within the arterial intima and its subsequent uptake by macrophages are the characteristic pathological hallmarks of atherosclerosis. As pivotal effector cells in this process, macrophages with their distinctive performances decisively determine the progression and resolution of atherosclerotic inflammation. The complete life cycle of macrophages in atherosclerotic plaques encompasses chemotaxis, infiltration, polarization, uptake of lipoproteins for metabolic efflux, foam cell formation, lipid overload, and various forms of programmed necrosis, including autophagy, pyroptosis, apoptosis, necrosis, and efferocytosis, to facilitate the removal of apoptotic macrophages and limit inflammation progression. The behavior of macrophages in atherosclerosis has rarely been comprehensively addressed in previous review articles. This article provides an extensive overview of the entire life cycle of macrophages following their response to atherosclerotic inflammation and the impact of regulatory factors on inflammation progression and resolution. Considering that macrophages play a pivotal role in the inflammatory response associated with atherosclerosis, targeting the regulation of their life cycle holds promise for therapeutic interventions against atherosclerosis-related cardiovascular diseases.