AUTHOR=Yurdagul Arif , Doran Amanda C. , Cai Bishuang , Fredman Gabrielle , Tabas Ira A. TITLE=Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=4 YEAR=2018 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2017.00086 DOI=10.3389/fcvm.2017.00086 ISSN=2297-055X 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.