Macrophage oxysterols and their binding proteins: roles in atherosclerosis.

To offer a comprehensive review on the roles that oxysterols synthesized or engulfed by macrophages, or oxysterol-binding proteins in these cells, play in the development and progression of atherosclerotic lesions. Oxysterols abundant within the plaque have the capacity to potentiate macrophage proinflammatory signaling and to induce cell death. These activities may contribute to formation of the complex lesion, expansion of the necrotic core, and to plaque rupture. On the contrary, several endogenous oxysterols generated by cholesterol hydroxylases act as ligands of liver X receptors, stimulate macrophage cholesterol efflux, repress proinflammatory signaling, and promote macrophage survival, counteracting lesion progression. Cytoplasmic oxysterol-binding proteins represent a family of sterol and phosphoinositide sensors that may contribute to the regulatory impact of these bioactive lipids on processes relevant in the context of atherogenesis. The generation and deposition of oxysterols within the developing plaque is envisioned to modulate macrophage lipid metabolism, to affect the delicate balance of proinflammatory and anti-inflammatory processes, and to impact cell fate decisions, thus, determining whether the lesion remains benign or whether it develops into a hazardous, vulnerable plaque.