Macrophage-Derived Foam Cells in Atherosclerosis: Lessons from Murine Models and Implications for Therapy

Macrophage-derived foam cells play integral roles in all stages of atherosclerosis. These lipid-laden immune cells are present from the earliest discernable fatty-streak lesions to advanced plaques, and are key regulators of the pathologic behavior of plaques. This review summarizes the current understanding of the molecular mechanisms that regulate macrophage cholesterol uptake, foam cell formation, and lipid-driven pro-inflammatory responses that promote atherosclerosis. Specific emphasis will be placed on recent findings from mouse models of atherosclerosis regarding the pathways of macrophage differentiation into foam cells and their implications for developing macrophage-directed therapeutic targets.