Absence of adipocyte fatty acid binding protein prevents the development of accelerated atherosclerosis in hypercholesterolemic mice

Lipid deposition in arterial walls due to elevated levels of plasma cholesterol is central to the development of atherosclerosis and involves the uptake of oxidized low‐density lipoprotein (oxLDL) by macrophages. Fatty acid binding proteins (FABPs) belong to a family of low molecular weight cytoplasmic proteins that are involved with intracellular transport and metabolism of fatty acids, and adipocyte FABP (aP2) has recently been shown to be expressed in macrophages. Here, we investigate the role of aP2 in the development of atherosclerosis in mice. We show that atherosclerotic lesions from hypercholesterolemic, apolipoprotein E deficient (ApoE −/− ) mice (but not arterial walls from normal mice) contain high levels of aP2 mRNA. We also identified aP2 in inflammatory cells that localized in these lesions, as confirmed by its presence in isolated mouse and human macrophages, and demonstrated that aP2 is induced by oxLDL. To determine the importance of aP2 in atherosclerosis, we generated mice lacking both ApoE and aP2 (ApoE −/− aP2 −/− ). In comparison with ApoE −/− mice, ApoE −/− aP2 −/− mice developed trivial lesions that were markedly smaller, less complex, and less macrophage‐rich even though the ApoE −/− aP2 −/− mice remained hypercholesterolemic. Absence of aP2 did not prevent lesion formation and macrophage accumulation in transplant‐associated arteriosclerosis that does not depend on elevated levels of cholesterol. These results indicate a critical role for aP2 in the development of hypercholesterolemia‐induced atherosclerosis.