Mechanisms of foam cell formation in atherosclerosis

J Mol Med (Berl). 2017 Nov;95(11):1153-1165. doi: 10.1007/s00109-017-1575-8. Epub 2017 Aug 7.


Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

Keywords: Atherosclerosis; Cholesterol; Endothelial cell; Foam cell; Macrophage; Smooth muscle cell; oxLDL.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / etiology*
  • Atherosclerosis / pathology*
  • Biological Transport
  • Cholesterol / metabolism
  • Endothelial Cells / metabolism
  • Foam Cells / immunology
  • Foam Cells / metabolism*
  • Foam Cells / pathology*
  • Humans
  • Lipid Metabolism
  • Lipoproteins, LDL / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • MicroRNAs / genetics
  • Myocytes, Smooth Muscle / metabolism


  • Lipoproteins, LDL
  • MicroRNAs
  • oxidized low density lipoprotein
  • Cholesterol