Novel insights: Dynamic foam cells derived from the macrophage in atherosclerosis

Abstract

Atherosclerosis can be regarded as a chronic disease derived from 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 atherosclerosis but also a key stage in 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 a new idea about foam cells in atherosclerosis.Rather than an isolated microenvironment, the macrophage multiple lipid uptake pathways, lipid internalization, lysosome, mitochondria, endoplasmic reticulum, neutral cholesterol ester hydrolase (NCEH), acyl-coenzyme A-cholesterol acyltransferase (ACAT), and reverse cholesterol transport are mutually influential, and form a dynamic process under multi-factor regulation. The macrophage takes on different uptake lipid statuses 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 is essential for physiology and pathology.Therefore, we propose that the foam cell in the process of atherosclerosis may be dynamic under multi-factor regulation, and collate this study to provide a holistic and dynamic idea of the foam cell. K E Y W O R D S acrophage, dynamic foam cell, lipoprotein internalization, lipoprotein uptake, reverse cholesterol transport 1 | INTRODUCTION Atherosclerosis (AS), a chronic inflammatory disease characterized by serum lipid metabolism disorder and excessive cholesterol loading macrophages in the blood vessel wall, is the main cause of cardiovascular disease, such as coronary artery disease, myocardial infarction, and stroke (

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