Lipid Metabolism in Macrophages: Focus on Atherosclerosis

Abstract

Mechanisms of lipid homeostasis and its impairment are of crucial importance for atherogenesis, and their understanding is necessary for successful development of new therapeutic approaches. In the arterial wall, macrophages play a prominent role in intracellular lipid accumulation, giving rise to foam cells that populate growing atherosclerotic plaques. Under normal conditions, macrophages are able to process substantial amounts of lipids and cholesterol without critical overload of the catabolic processes. However, in atherosclerosis, these pathways become inefficient, leading to imbalance in cholesterol and lipid metabolism and disruption of cellular functions. In this review, we summarize the existing knowledge on the involvement of macrophage lipid metabolism in atherosclerosis development, including both the results of recent studies and classical concepts, and provide a detailed description of these processes from the moment of lipid uptake with lipoproteins to cholesterol efflux.

Metformin, Macrophage Dysfunction and Atherosclerosis

“…Lowering LDL plasma levels is a first line clinical treatment to decrease the risk profile of patients for cardiovascular and cerebrovascular diseases (7,9). In the initial stage of the development of atherosclerotic lesions, plasma lipoproteins trapped by modified proteoglycans accumulate in the subendothelial space, which can cause endothelial cell (EC) and platelet activation (8)(9)(10)(11)(12). Circulating monocytes adhere to the activated endothelium, penetrate the endothelium and differentiate into pro-inflammatory macrophages, which form foam cells by increasing the uptake of oxLDL.…”

“…Circulating monocytes adhere to the activated endothelium, penetrate the endothelium and differentiate into pro-inflammatory macrophages, which form foam cells by increasing the uptake of oxLDL. This aggravated inflammation expands as foam cells spread over the growing atheroma ( 9 , 10 ). The process of AS is accelerated by numerous factors, such as the generation of ROS, as well as the release of inflammatory chemokines and cytokines ( 9 , 13 ).…”

Apolipoprotein M promotes cholesterol uptake and efflux from mouse macrophages

“…Another explanation is that in the WT group, the rate of cholesterol influx becomes too high and mechanisms of cholesterol homeostasis regulation do not function properly, which can lead to endoplasmic reticulum (ER) stress initiation. One consequence of ER stress is the downregulation of ABCA1, which leads to foam cell formation [48,49]. From the current data, we can see that ApoM deletion affects the expression of cholesterol transport‐related genes in the process of cholesterol uptake.…”

High-throughput screening of circRNAs reveals novel mechanisms of tuberous sclerosis complex-related renal angiomyolipoma

“…The AMACR gene encodes an enzyme which regulates β-oxidation of branched chain lipids in peroxisomes and mitochondria and promotes chiral reversal of 2-methyl acids [25]. The LAMP2 gene encodes the lysosomal-associated membrane protein 2, which facilitates the transport of cholesterol [26]. Therefore, cir-cRNAs may play an important role in the regulation of lipid metabolism in TSC-RAML, and circRNA_025332 may be a potential target for lipid metabolism targeting therapy.…”