TY - JOUR
T1 - Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis
AU - Yurdagul, Arif
AU - Doran, Amanda C.
AU - Cai, Bishuang
AU - Fredman, Gabrielle
AU - Tabas, Ira A.
N1 - Publisher Copyright:
© Copyright © 2018 Yurdagul, Doran, Cai, Fredman and Tabas.
PY - 2018/1/8
Y1 - 2018/1/8
N2 - 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.
AB - 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.
KW - atherosclerosis
KW - efferocytosis
KW - inflammation resolution
KW - macrophages
KW - post-apoptotic necrosis
UR - http://www.scopus.com/inward/record.url?scp=85051112214&partnerID=8YFLogxK
U2 - 10.3389/fcvm.2017.00086
DO - 10.3389/fcvm.2017.00086
M3 - Review article
AN - SCOPUS:85051112214
SN - 2297-055X
VL - 4
JO - Frontiers in Cardiovascular Medicine
JF - Frontiers in Cardiovascular Medicine
M1 - 86
ER -