Lack of macrophage fatty-acid-binding protein aP2 protects mice deficient in apolipoprotein E against atherosclerosis

The adipocyte fatty-acid-binding protein, aP2, has an important role in reg ulating systemic insulin resistance and lipid metabolism. Here we demonstra te that aP2 is also expressed in macrophages, has a significant role in the ir biological responses and contributes to the development of atheroscleros is. Apolipoprotein E (ApoE)-deficient mice also deficient for aP2 showed pr otection from atherosclerosis in the absence of significant differences in serum lipids or insulin sensitivity. aP2-deficient macrophages showed alter ations in inflammatory cytokine production and a reduced ability to accumul ate cholesterol esters when exposed to modified lipoproteins. Apoe(-/-) mic e with Ap2(+/+) adipocytes and Ap2(-/-) macrophages generated by bone-marro w transplantation showed a comparable reduction in atherosclerotic lesions to those with total aP2 deficiency, indicating an independent role for macr ophage aP2 in atherogenesis. Through its distinct actions in adipocytes and macrophages, aP2 provides a link between features of the metabolic syndrom e and could be a new therapeutic target for the prevention of atheroscleros is.