Role of macrophage-expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice

Atherosclerosis is an inflammatory disease process associated with elevated levels of plasma cholesterol, especially low-density lipoproteins. The lat ter become trapped within the arterial wall and are oxidized and taken up b y macrophages to form foam cells. This process is an initiating event for a therosclerosis. Fatty acid binding proteins (FABP) are involved in fatty ac id metabolism and cellular lipid transport, and adipocyte FABP (aP2) is als o expressed in macrophages. We recently generated mice lacking both apolipo protein (Apo) E and aP2 (ApoE(-/-) aP2(-/-)) and found that these mice, com pared with ApoE(-/-) mice, developed markedly smaller atherosclerotic lesio ns that contained fewer macrophages. Here we investigated the mechanism(s) responsible for this prevention of atherosclerotic lesion formation. Bone m arrow transplantations were performed in ApoE(-/-) mice, receiving cells fr om either ApoE(-/-) or ApoE(-/-) aP2(-/-) mice. The lack of aP2 in donor ma rrow cells led to the development of smaller (5.5-fold) atherosclerotic les ions in the recipient mice. No differences were found in plasma cholesterol , glucose, or insulin levels between recipients of bone marrow cells from A poE(-/-) or ApoE(-/-) aP2(-/-) mice. However, the expression of chemoattrac tant and inflammatory cytokines was decreased in macrophages from ApoE(-/-) aP2(-/-) mice compared with ApoE(-/-) mice, which may contribute to the de crease in atherosclerotic lesion formation. Taken together, we demonstrate the importance of macrophage aP2 in the development of atherosclerotic lesi ons.