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 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.
Layne
M D
MD
Program of Developmental Cardiovascular Biology, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Patel
A
A
Chen
Y H
YH
Rebel
V I
VI
Carvajal
I M
IM
Pellacani
A
A
Ith
B
B
Zhao
D
D
Schreiber
B M
BM
Yet
S F
SF
Lee
M E
ME
Storch
J
J
Perrella
M A
MA
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications / Q000473:pathology*; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006937:Hypercholesterolemia / Q000150:complications*; D007328:Insulin / Q000097:blood; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide / Q000097:blood
D001057:Apolipoproteins E; D001786:Blood Glucose; D002352:Carrier Proteins; D016207:Cytokines; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D007328:Insulin; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009569:Nitric Oxide; D002784:Cholesterol