Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis

Arif Yurdagul, Amanda C. Doran, Bishuang Cai, Gabrielle Fredman, Ira A. Tabas

Research output: Contribution to journalReview articlepeer-review

125 Scopus citations

Abstract

Efficient clearance of apoptotic cells, termed efferocytosis, critically regulates normal homeostasis whereas defective uptake of apoptotic cells results in chronic and non-resolving inflammatory diseases, such as advanced atherosclerosis. Monocyte-derived macrophages recruited into developing atherosclerotic lesions initially display efficient efferocytosis and temper inflammatory responses, processes that restrict plaque progression. However, during the course of plaque development, macrophages undergo cellular reprogramming that reduces efferocytic capacity, which results in post-apoptotic necrosis of apoptotic cells and inflammation. Furthermore, defective efferocytosis in advanced atherosclerosis is a major driver of necrotic core formation, which can trigger plaque rupture and acute thrombotic cardiovascular events. In this review, we discuss the molecular and cellular mechanisms that regulate efferocytosis, how efferocytosis promotes the resolution of inflammation, and how defective efferocytosis leads to the formation of clinically dangerous atherosclerotic plaques.

Original languageEnglish
Article number86
JournalFrontiers in Cardiovascular Medicine
Volume4
DOIs
StatePublished - 8 Jan 2018
Externally publishedYes

Keywords

  • atherosclerosis
  • efferocytosis
  • inflammation resolution
  • macrophages
  • post-apoptotic necrosis

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