Mechanism of efferocytosis in atherosclerosis

J Mol Med (Berl). 2024 Jul;102(7):831-840. doi: 10.1007/s00109-024-02439-3. Epub 2024 May 10.

Abstract

Atherosclerosis (AS) is a chronic inflammatory vascular disease that occurs in the intima of large and medium-sized arteries with the immune system's involvement. It is a common pathological basis for high morbidity and mortality of cardiovascular diseases. Abnormal proliferation of apoptotic cells and necrotic cells leads to AS plaque expansion, necrotic core formation, and rupture. In the early stage of AS, macrophages exert an efferocytosis effect to engulf and degrade apoptotic, dead, damaged, or senescent cells by efferocytosis, thus enabling the regulation of the organism. In the early stage of AS, macrophages rely on this effect to slow down the process of AS. However, in the advanced stage of AS, the efferocytosis of macrophages within the plaque is impaired, which leads to the inability of macrophages to promptly remove the apoptotic cells (ACs) from the organism promptly, causing exacerbation of AS. Moreover, upregulation of CD47 expression in AS plaques also protects ACs from phagocytosis by macrophages, resulting in a large amount of residual ACs in the plaque, further expanding the necrotic core. In this review, we discussed the molecular mechanisms involved in the process of efferocytosis and how efferocytosis is impaired and regulated during AS, hoping to provide new insights for treating AS.

Keywords: Apoptotic cells; Atherosclerosis; CD47; Efferocytosis; Macrophages.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Atherosclerosis* / metabolism
  • Atherosclerosis* / pathology
  • CD47 Antigen / metabolism
  • Efferocytosis
  • Humans
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Necrosis
  • Phagocytosis*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology

Substances

  • CD47 Antigen