TY - JOUR
T1 - Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia
AU - Boord, Jeffrey B.
AU - Maeda, Kazuhisa
AU - Makowski, Liza
AU - Babaev, Vladimir R.
AU - Fazio, Sergio
AU - Linton, MacRae F.
AU - Hotamisligil, Gökhan S.
PY - 2002/10/1
Y1 - 2002/10/1
N2 - Objective - The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Methods and Results - Mice deficient in aP2 and apolipoprotein E (aP2-/-apoE-/- mice) and apolipoprotein E-deficient control mice (apoE-/- mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE-/- control mice, male and female aP2-/-apoE-/- mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. Conclusions - These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.
AB - Objective - The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Methods and Results - Mice deficient in aP2 and apolipoprotein E (aP2-/-apoE-/- mice) and apolipoprotein E-deficient control mice (apoE-/- mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE-/- control mice, male and female aP2-/-apoE-/- mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. Conclusions - These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.
KW - Atherosclerosis
KW - Fatty acid-binding protein
KW - Insulin resistance
KW - Mice
KW - aP2
UR - http://www.scopus.com/inward/record.url?scp=0036790535&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036790535&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000033090.81345.E6
DO - 10.1161/01.ATV.0000033090.81345.E6
M3 - Article
C2 - 12377750
AN - SCOPUS:0036790535
SN - 1079-5642
VL - 22
SP - 1686
EP - 1691
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 10
ER -