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Role of macrophage‐expressed adipocyte fatty acid binding protein in the development of accelerated atherosclerosis in hypercholesterolemic mice
Author(s) -
Layne Matthew D.,
Patel Anand,
Chen Yen-Hsu,
Rebel Vivienne I.,
Carvajal Irvith M.,
Pellacani Andrea,
Ith Bonna,
Zhao Dezheng,
Schreiber Barbara M.,
Yet Shaw-Fang,
Lee Mu-En,
Storch Judith,
Perrella Mark A.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0374fje
Subject(s) - apolipoprotein e , macrophage , endocrinology , bone marrow , medicine , lesion , foam cell , cholesterol , adipocyte , apolipoprotein b , inflammation , chemistry , biology , lipoprotein , biochemistry , pathology , adipose tissue , in vitro , disease
Atherosclerosis is an inflammatory disease process associated with elevated levels of plasma cholesterol, especially low‐density lipoproteins. The latter become trapped within the arterial wall and are oxidized and taken up by macrophages to form foam cells. This process is an initiating event for atherosclerosis. Fatty acid binding proteins (FABP) are involved in fatty acid metabolism and cellular lipid transport, and adipocyte FABP (aP2) is also expressed in macrophages. We recently generated mice lacking both apolipoprotein (Apo)E and aP2 (ApoE −/− aP2 −/− ) and found that these mice, compared with ApoE −/− mice, developed markedly smaller atherosclerotic lesions that contained fewer macrophages. Here we investigated the mechanism(s) responsible for this prevention of atherosclerotic lesion formation. Bone marrow transplantations were performed in ApoE −/− mice, receiving cells from either ApoE −/− or ApoE −/− aP2 −/− mice. The lack of aP2 in donor marrow cells led to the development of smaller (5.5‐fold) atherosclerotic lesions in the recipient mice. No differences were found in plasma cholesterol, glucose, or insulin levels between recipients of bone marrow cells from ApoE −/− or ApoE −/− aP2 −/− mice. However, the expression of chemoattractant and inflammatory cytokines was decreased in macrophages from ApoE −/− aP2 −/− mice compared with ApoE −/− mice, which may contribute to the decrease in atherosclerotic lesion formation. Taken together, we demonstrate the importance of macrophage aP2 in the development of atherosclerotic lesions.