Novel insights: Dynamic foam cells derivedfrom the macrophage in atherosclerosis.

Abstract

Atherosclerosis can be regarded as a chronic disease derivedfrom the interaction between disordered lipoproteins and an unsuitable immune response. The evolution of foam cells is not only a significant pathological change in the early stage of atherosclerosisbut also a key stagein the occurrence and development of atherosclerosis. The formation of foam cells is mainly caused by the imbalance among lipids uptake, lipids treatment, and reverse cholesterol transport. Although a large number of studies have summarized the source of foam cells and the mechanism of foam cells formation, we propose anew ideaabout foam cells in atherosclerosis. Rather than an isolated microenvironment,the macrophage multiple lipiduptake pathways, lipidinternalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, andforma dynamic process under multi-factor regulation. The macrophage takes on different uptake lipidstatuses depending on multiple uptake pathways and intracellular lipids, lipid metabolites versus pro-inflammatory factors. Except for NCEH and ACAT, the lipid internalization of macrophages also depends on multicellular organelles including the lysosome, mitochondria, and endoplasmic reticulum, which are associated with each other. A dynamic balance between esterification and hydrolysis of cholesterol for macrophages isessential for physiology and pathology. Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamicunder multi-factor regulation, and collate thisstudy to provide a holistic and dynamic idea ofthe foam cell.