Scavenger receptors: friend or foe in atherosclerosis?

Scavenger receptors were originally defined by their ability to bind and internalize modified lipoproteins. Nowadays the family of scavenger receptors is composed of structurally different surface receptors which recognize a broad pattern of common ligands which include, besides modified lipoproteins, apoptotic cells and pathogens. This review focuses on the role of scavenger receptors in the development of atherosclerotic lesions.

Recent studies indicate that scavenger receptor A activity can be regulated by phosphorylation, glucosidases, 8-isoprostane, high glucose and nobiletin. Modulation of these regulatory components may beneficially influence scavenger receptor A's proatherogenic function. It appears that statins do lead to a reduction in CD36 transcription and could modulate in this way CD36-mediated atherosclerotic foam cell formation. Macrophage scavenger receptor BI appears to facilitate the development of small fatty streak lesions, whereas the formation of advanced atherosclerotic lesions is reduced, indicating a unique dual role for macrophage scavenger receptor BI in the pathogenesis of atherosclerosis.

It is proposed that the presence of scavenger receptors in macrophages is beneficial because they remove potential deleterious material from the arterial wall. Inadequate handling of the internalized material by the macrophages will lead to foam cell formation. If adequate levels of ATP-binding cassette transporters and accepting HDL are present, however, the macrophage is perfectly able to metabolize and secrete the internalized atherogenic substances whereby HDL facilitates further transport from the arterial wall to the liver, leading to release in bile.