During the growing process of the atherosclerotic lesions, lipid-filled macrophage foam cells form, accumulate, and ultimately undergo apoptotic death. If the apoptotic foam cells are not timely removed, they may undergo secondary necrosis, and form a necrotic lipid core which renders the plaque unstable and susceptible to rupture. Therefore, the non-lipid-filled fellow macrophages, as the main phagocytic cells in atherosclerotic lesions, need to effectively remove the apoptotic foam cells. In general, in apoptotic macrophages, caspases are the central regulators of several key processes required for their efficient efferocytosis. The processes include the generation of "Find-Me" signals (such as adenosine triphosphate/uridine triphosphate, fractalkine, lysophosphatidylcholine, and sphingosine-1-phosphate) for the recruitment of viable macrophages, generation of the "Eat-Me" signals (for example, phosphatidylserine) for the engulfment process, and, finally, release of anti-inflammatory mediators (including transforming factor β and interleukin-10) as a tolerance-enhancing and an anti-inflammatory response, and for the motile behavior of the apoptotic cell. The caspase-dependent mechanisms are operative also in apoptotic macrophages driving the atherogenesis. In this review, we explore the role of the molecular pathways related to the caspase-dependent events in efferocytosis in the context of atherosclerosis. Understanding of the molecular mechanisms of apoptotic cell death in atherosclerotic lesions is essential when searching for new leads to treat atherosclerosis.
Keywords: Apoptosis; Atherosclerosis; Necrosis; Phagocytic cells; Plaque rupture; Reactive oxygen species.
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