MicroRNA sequences modulating inflammation and lipid accumulation in macrophage “foam” cells: Implications for atherosclerosis

Abstract

Accumulation of macrophage “foam” cells, laden with cholesterol and cholesteryl ester, within the intima of large arteries, is a hallmark of early “fatty streak” lesions which can progress to complex, multicellular atheromatous plaques, involving lipoproteins from the bloodstream and cells of the innate and adaptive immune response. Sterol accumulation triggers induction of genes encoding proteins mediating the atheroprotective cholesterol efflux pathway. Within the arterial intima, however, this mechanism is overwhelmed, leading to distinct changes in macrophage phenotype and inflammatory status. Over the last decade marked gains have been made in understanding of the epigenetic landscape which influence macrophage function, and in particular the importance of small non-coding micro-RNA (miRNA) sequences in this context. This review identifies some of the miRNA sequences which play a key role in regulating “foam” cell formation and atherogenesis, highlighting sequences involved in cholesterol accumulation, those influencing inflammation in sterol-loaded cells, and novel sequences and pathways which may offer new strategies to influence macrophage function within atherosclerotic lesions.

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

“…Thus, inflammation is entangled with many other processes related for example to blood pressure, hormonal balance, central and peripheral nervous system function, metabolism. With respect to lipid metabolism, inflammation impacts on the levels and composition of circulating lipoproteins and on cell cholesterol homeostasis through the regulation of cell cholesterol transporters [ 174 , 175 ]. However, such a relationship appears to be bidirectional, as dysfunctional serum lipoproteins, particularly HDL, and cell cholesterol unbalance may be important factors generating or amplifying pro-inflammatory signals [ 81 , 176 ].…”

Metformin suppresses foam cell formation, inflammation and ferroptosis via the AMPK/ERK signaling pathway in ox‑LDL‑induced THP‑1 monocytes

“…Foam cell formation is an essential factor in the progression of atherosclerosis (29). The foam cells under the endothelium tend to secrete inflammatory factors to promote local inflammation and the development of an immune response, thereby facilitating the formation of atherosclerotic plaques that contribute to the manifestation of symptoms and inhibit the recovery of patients with atherosclerosis (30).…”

MicroRNA expression profile of cholesterol metabolism analysis mediated by Thelenota ananas desulfated holothurin A saponin in RAW264.7 macrophage-foam cells

“…23 In macrophages, miRNAs play an important role in polarization, inflammatory response, and related cytokine production and regulate cholesterol metabolism and foam cell formation, which make them a suitable therapeutic target. 24,25 Therefore, we selected oxLDL-stimulated macrophage-foam cells as a cell model, since oxLDL is a major pro-inflammatory factor in the development of AS, and then used high-throughput sequencing technology to detect the miRNA species and differential expression associated with AS.…”