The role of macrophage aP2 in atherosclerosis

Adipocyte fatty-acid–binding protein (aP2) has an established role in regulating systemic insulin resistance and lipid metabolism. In May Nature Medicine, Liza Makowski and colleagues from Harvard School of Public Health, Boston, demonstrate that aP2 is also expressed in macrophages and has a role in the development of atherosclerosis.

Makowski et al showed that transgenic mice lacking apolipoprotein E (ApoE), which normally develop complex atherosclerotic lesions, were protected from atherosclerosis if they were concomitantly lacking aP2 (in the absence of significant differences in serum lipids or insulin sensitivity). In addition, aP2-deficient macrophages showed alterations in inflammatory cytokine production and a reduced ability to accumulate cholesterol esters when exposed to modified lipoproteins. Apoe^-/-mice with Ap2^+/+adipocytes and Ap2^-/-macrophages generated by bone-marrow transplantation had a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macrophage aP2 in atherogenesis (Nature Med 2001, 7:699-705).

These data support a coordinated ...