Cor Vasa 2019, 61(1):48-55 | DOI: 10.1016/j.crvasa.2018.06.006

Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

Alexandrina Volobueva^a, Dongwei Zhang^b, Andrey V. Grechko^c, Alexander N. Orekhov^d,e

^a Laboratory of Gene Therapy, Biocad Biotechnology Company, 198515 Saint-Petersburg, Russia

^b Diabetes Research Center, Traditional Chinese Medicine School, Beijing University of Chinese Medicine, 100029 Beijing, China

^c Federal Scientific Clinical Center for Resuscitation and Rehabilitation, 109240 Moscow, Russia

^d Institute for Atherosclerosis Research, Skolkovo Innovative Center, 121609 Moscow, Russia

^e Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia

Foam cells are typical components of atherosclerotic plaques, where they actively participate in the intracel- lular cholesterol accumulation. Onset and further progression of atherosclerosis is tightly associated with foam cell formation. These cells can originate both from the circulating monocytes/macrophages and from the resident smooth muscular cells migrating to the growing lesion. Classically activated pro-inflammatory M1 macrophages play an important role in atherogenesis, while M2 macrophages have a protective role in plaque stabilization. Molecular mechanisms for VSMC transformation towards foam cells remains to be studied in detail. Lipid droplets filling the foam cells are generated from metabolized modified low-density lipoproteins (LDL). LDL serves as the main source or lipids, which penetrate the endothelium both via LDL-receptor-dependent and alternative ALK-1-regulated pathways. Under pathologic conditions, LDL can undergo modification, such as sialylation, oxidation, glycation or carbamylation, leading to its excessive uptake by macrophages infiltrating the subendothelial space. Modified LDL is recognized mainly by scavenger receptors, such as SR-A1, CD36, LOX-1, CD68, those expression is low under physiological conditions and can be upregulated via JNK, Wnt and NF-κB signaling. In foam cells LDL is digested to fatty acids and free cholesterol. Cholesterol can be esterified and further hydrolyzed for efflux to poorly lipidated ApoA-I or mature HDL. In this review, we discuss the basic concepts in foam cell formation established so far, as well as different aspects of cholesterol uptake, metabolism and efflux disturbances in atherosclerosis.

Keywords: Atherosclerosis, Cholesterol accumulation, Foam cells, LDL

Received: May 7, 2018; Revised: June 24, 2018; Accepted: June 26, 2018; Published: March 21, 2019  Show citation