Atherosclerosis is a dynamic and progressive inflammatory process in the intimal layer of large and medium-sized arteries, and it is the major contributor to the atherosclerotic cardiovascular disease (ACVD), the leading cause of death worldwide. In an atherosclerotic plaque, phagocytosis of apoptotic cells occurs through an intricate process designated efferocytosis. Defective efferocytosis has emerged as a causal factor in the etiopathogenesis of atherosclerosis and its progression into overt ACVD. Both specialized phagocytes (macrophages and dendritic cells) and non-specialized cells with phagocytic capabilities (smooth muscle and endothelial cells) are involved in the efferocytotic process. Moreover, several signaling and regulatory molecules are involved in the different steps of efferocytosis, and they include “Find-Me” signals (lysophosphatidylcholine), “Eat-Me” signals [phosphatidylserine, Mer tyrosine kinase (MerTK), and milk fat globule-EGF factor 8], and “Don't Eat-Me” signals [cluster of differentiation 47 (CD47)]. Regulation of efferocytosis is in a close nexus with inflammation, the key component in atherosclerosis. The predominance of pro-inflammatory and anti-inflammatory molecules plays a crucial role in lesion progression and regression, respectively. Polarization of macrophages towards the M1 phenotype causes them to secrete proinflammatory cytokines, while polarization towards the M2 phenotype causes them to secrete of anti-inflammatory cytokines, including interleukin-10 and transforming growth factor β, so tending to shift the balance towards resolution of the inflammation. Dysfunction of any regulatory signal may cause expansion of the necrotic core of an atherosclerotic plaque with ensuing conversion of the plaque into an unstable plaque with an increased susceptibility to rupture and to atherothrombotic complication. In this review we aim at elucidating the determinant factors and pathways of efferocytosis which can be considered as potential novel targets when striving to develop more personalized and efficient treatment regimens for patients with ACVD.

动脉粥样硬化是大中型动脉内膜层的动态和进行性炎症过程，它是导致全球死亡的主要原因动脉粥样硬化性心血管疾病（ACVD）的主要因素。在动脉粥样硬化斑块中，凋亡细胞的吞噬作用是通过复杂的过程（称为胞吞作用）发生的。缺陷性红细胞增多症已成为动脉粥样硬化病因及其发展为明显的ACVD的病因。特异的吞噬细胞（巨噬细胞和树突状细胞）和具有吞噬功能的非特异细胞（平滑肌和内皮细胞）均参与胞吞过程。此外，几种信号传导和调节分子参与了胞吞的不同步骤，其中包括“ Find-Me”信号（溶血磷脂酰胆碱），“ Eat-Me”信号[磷脂酰丝氨酸，Mer酪氨酸激酶（MerTK）和牛奶脂肪球-EGF因子8]和“ Do n't Eat-Me”信号[分化簇47（CD47）]。血细胞增多症的调节与炎症密切相关，炎症是动脉粥样硬化的关键因素。促炎和抗炎分子的优势分别在病变进展和消退中起关键作用。巨噬细胞朝向M1表型的极化导致它们分泌促炎细胞因子，而朝向M2表型的极化导致它们分泌抗炎细胞因子（包括白介素10和转化生长因子β），因此趋向于将平衡转移至解决炎。任何调节信号的功能障碍都可能导致动脉粥样硬化斑块的坏死核心扩张，从而导致斑块转变为不稳定的斑块，从而增加了破裂和动脉粥样硬化并发症的易感性。在这篇综述中，我们旨在阐明在努力为ACVD患者开发更个性化和有效的治疗方案时，可以考虑的确定性因素和有效的细胞增生途径。