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 cholest erol is central to the development of atherosclerosis and involves the upta ke of oxidized low-density lipoprotein (oxLDL) by macrophages. Fatty acid b inding proteins (FABPs) belong to a family of low molecular weight cytoplas mic proteins that are involved with intracellular transport and metabolism of fatty acids, and adipocyte FABP (aP2) has recently been shown to be expr essed in macrophages. Here, we investigate the role of aP2 in the developme nt of atherosclerosis in mice. We show that atherosclerotic lesions from hy percholesterolemic, apolipoprotein E deficient (ApoE(-/-)) mice (but not ar terial walls from normal mice) contain high levels of aP2 mRNA. We also ide ntified aP2 in inflammatory cells that localized in these lesions, as confi rmed by its presence in isolated mouse and human macrophages, and demonstra ted that aP2 is induced by oxLDL. To determine the importance of aP2 in ath erosclerosis, we generated mice lacking both ApoE and aP2 (ApoE(-/-) aP2(-/ -)). In comparison with ApoE(-/-) mice, ApoE(-/-)aP2(-/-) mice developed tr ivial 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 accumulatio n in transplant-associated arteriosclerosis that does not depend on elevate d levels of cholesterol. These results indicate a critical role for aP2 in the development of hypercholesterolemia-induced atherosclerosis.