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The macrophage foam cell as a target for therapeutic intervention

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Specialized functions of macrophages have evolved to protect the body from infection. However, the same mechanisms that enable phagocytosis of pathogens and activation of leukocytes also permit the uptake of lipoproteins and release of reactive oxygen species and immune mediators that collectively contribute to atherosclerosis. New approaches to inhibit lipid accumulation in macrophage foam cells and reduce inflammatory responses may be of therapeutic value in preventing coronary artery disease.

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Acknowledgements

Because of space limitations, we were unable to cite all of the primary sources of data discussed in this review. We thank J.L. Witztum for comments and A. Zulueta for assistance with preparation of the manuscript. We thank the Stanford University Donald W. Reynolds Center and National Institutes of Health grants to the La Jolla Specialized Center for Research on Molecular Medicine and Atherosclerosis for support.

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Correspondence to Christopher K. Glass.

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Further reading

Figure 1: Photomicrograph of a macrophage foam cell isolated from a hypercholesterolemic mouse.
Figure 2: Mechanisms contributing to the recruitment of monocytes to the artery wall and their differentiation into macrophages.

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Figure 3: Mechanisms contributing to foam-cell formation.

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Figure 4: Mechanisms that act to protect cells from toxic effects of free cholesterol.

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Figure 5: Interactions of macrophages with Th1 and Th2 cells that influence the development of atherosclerosis.

D. Maizels