Macrophage differentiation to foam cells

Pavel Shashkin, Bojan Dragulev, Klaus Ley

Research output: Contribution to journalReview articlepeer-review

230 Scopus citations

Abstract

Foam cell formation from macrophages with subsequent fatty streak formation plays a key role in early atherogenesis. Foam cell formation is thought to be induced by Low Density Lipoproteins (LDL), including oxidized LDL (OxLDL) or minimally modified LDL (mmLDL). Understanding the molecular mechanisms involved in OxLDL- and mmLDL-induced foam cell formation is of fundamental importance for atherosclerosis and cardiovascular disease. The expression of many genes is likely modulated during macrophage transformation into a foam cell. In this mini-review we describe functional consequences of modulation of three groups of genes: Scavenger Receptors (SR-A, CLA-1/SR-B1, CD36, CD68, LOX-1, and SR-PSOX), the PPAR family of nuclear receptors, and a number of genes involved in eicosanoid biosynthesis, including lipoxygenases and leukotriene receptors. Scavenger receptors appear to play a key role in uptake of OxLDL, while mmLDL appears to interact with CD14/TLR4. The regulation of scavenger receptors is, in part, mediated by the PPAR family of nuclear receptors. PPARα and PPARγ agonists, such as thiazolidinediones and fibrates, and PPARδ agonists were tested as atheroprotective drugs and showed some beneficial effects. Eicosanoids are naturally occuring agonists for PPARs. Recent observations indicate a role of the components of the eicosanoid cascade, such as 5-lipoxygenase, 15-lipoxygenase and the leukotriene receptors in foam cell formation. Selective inhibitors of lipoxygenases and leukotriene receptors could be useful in the treatment of atherosclerosis by preventing or reducing foam cell formation.

Original languageEnglish (US)
Pages (from-to)3061-3072
Number of pages12
JournalCurrent Pharmaceutical Design
Volume11
Issue number23
DOIs
StatePublished - 2005
Externally publishedYes

Keywords

  • Foam cells
  • Human
  • LDL
  • Leukotrienes
  • Lipoxygenase
  • Monocytes/macrophages
  • PPAR
  • Scavenger receptors

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Fingerprint

Dive into the research topics of 'Macrophage differentiation to foam cells'. Together they form a unique fingerprint.

Cite this