The pathological progression of atherosclerotic plaques depends on the presence and activity of macrophages. In Nature Medicine, Swirski and colleagues study mice deficient in apolipoprotein E to investigate the relative contributions of monocyte influx and in situ proliferation to the accumulation of macrophages in atherosclerotic plaques. Through the use of a parabiosis approach, they find that although the recruitment of monocytes is ultimately required for plaque seeding, the bulk of macrophages in the plaque can be accounted for by localized proliferation. Depletion of monocytes has minimal effect on macrophage numbers in established plaques, but inhibiting proliferation with the chemotherapeutic agent 5-fluorouracil diminishes lesion size. The contribution of localized macrophage proliferation to human atherosclerotic plaques remains to be determined; however, inhibiting proliferation with cytostatic drugs may be a useful therapeutic approach.

Nat. Med. (11 August 2013) doi:10.1038/nm.3258