Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms

Abstract

Foam cells play a vital role in the initiation and development of atherosclerosis. This review aims to summarize the novel insights into the origins, consequences, and molecular mechanisms of foam cells in atherosclerotic plaques. Foam cells are originated from monocytes as well as from vascular smooth muscle cells (VSMC), stem/progenitor cells, and endothelium cells. Novel technologies including lineage tracing and single-cell RNA sequencing (scRNA-seq) have revolutionized our understanding of subtypes of monocyte- and VSMC-derived foam cells. By using scRNA-seq, three main clusters including resident-like, inflammatory, and triggering receptor expressed on myeloid cells-2 (Trem2hi) are identified as the major subtypes of monocyte-derived foam cells in atherosclerotic plaques. Foam cells undergo diverse pathways of programmed cell death including apoptosis, autophagy, necroptosis, and pyroptosis, contributing to the necrotic cores of atherosclerotic plaques. The formation of foam cells is affected by cholesterol uptake, efflux, and esterification. Novel mechanisms including nuclear receptors, non-coding RNAs, and gut microbiota have been discovered and investigated. Although the heterogeneity of monocytes and the complexity of non-coding RNAs make obstacles for targeting foam cells, further in-depth research and therapeutic exploration are needed for the better management of atherosclerosis.

Protective interaction of human phagocytic APC subsets with Cryptococcus neoformans induces genes associated with metabolism and antigen presentation

“…Through the scavenger receptors MARCO and CXCL16, intracellular lipid concentration is increased (possibly creating foam cells) which triggers FABP4 (95,96). This then activates inflammation through both the IKK-NF-kb and JNK-AP-1 pathways (97,98).…”

“…This is also accompanied by increases in fatty acid metabolism through FABP4 which then acts as a link between this metabolism and inflammation ( 94 ). Through the scavenger receptors MARCO and CXCL16, intracellular lipid concentration is increased (possibly creating foam cells) which triggers FABP4 ( 95 , 96 ). This then activates inflammation through both the IKK-NF-κβ and JNK-AP-1 pathways ( 97 , 98 ).…”

Steroid hormone imbalance drives macrophage infiltration andSpp1/osteopontin+foam cell differentiation in the prostate

“…Our study is the first to report foam cell formation in benign prostate, which may be a particularly important step in the initiation of pathological changes. Foam cells have been implicated to drive inflammation and disease progression in atherosclerosis (19) and lung fibrosis (20). The infiltration of macrophages and their transition to foam cells drives the formation of the necrotic core of the plaque which eventually leads to the development of atherosclerotic lesions (19).…”

High Uric Acid Promotes Atherosclerotic Plaque Instability by Apoptosis Targeted Autophagy

“…Decades of research have established atherosclerosis as a chronic inflammatory disease 14) . Macrophages engulf lipoprotein and transform into foam cells, which undergo intricate kinds of death and impact the plaque stability [15][16][17] . Accumulating evidence suggests that defective autophagy has a detrimental effect on cardiovascular diseases 17) .…”