Rac1 and cholesterol metabolism in macrophage.

In the early stages of atherosclerotic lesion development, cholesterol is mostly present as esterified cholesterol stored in macrophage cytoplasmic lipid droplets. However, when the lesion evolves, free cholesterol accumulates in other compartments, such as lysosomes and plasma membrane. A number of studies support a role for intracellular cholesterol content and distribution in regulating several cell functions. Particularly, membrane free cholesterol content has a specific effect on signaling pathways involved in regulating cell motility and organization of the actin cytoskeleton. These processes are regulated by several signaling pathways including the small GTPase Rac1. Rac1 belongs to the Rho GTPases of the Ras protein superfamily involved in the regulation of multiple cell functions, including cell proliferation, chemotaxis, phagocytosis, degranulation, and superoxide production. In this review, we discuss the role of Rac1 in macrophage with respect to cholesterol metabolism and trafficking as critical aspects for the development of atherosclerotic plaque.