on August 4, 2003
Circulation. 2003
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000086981.09834.E0
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000086981.09834.E0
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Submitted on March 11, 2003
From the Departments of Medicine (Y.Z., M.R., D.J.R.) and Cell and Developmental Biology (Y.Z., I.Z., J.M.G.) and the Center for Experimental Therapeutics (Y.Z., M.R., D.J.R.), University of Pennsylvania School of Medicine, Philadelphia, Pa; and the Children's Hospital of Philadelphia (I.Z., G.H.R.), Philadelphia, Pa. * To whom correspondence should be addressed. E-mail: rader{at}mail.med.upenn.edu.
Background--Abundant data indicate that overexpression of apolipoprotein A-I (apoA-I) in mice inhibits atherosclerosis. One mechanism is believed to be promotion of reverse cholesterol transport, but no direct proof of this concept exists. We developed a novel approach to trace reverse transport of labeled cholesterol specifically from macrophages to the liver and feces in vivo and have applied this approach to investigate the ability of apoA-I overexpression to promote macrophage-specific reverse cholesterol transport. Methods and Results--J774 cells were loaded with cholesterol by incubation with acetylated LDL, labeled with 3H-cholesterol, and then injected intraperitoneally into mice. Plasma and feces were collected at 24 hours and 48 hours, when mice were exsanguinated, tissues were harvested, and all were analyzed for tracer counts. 3H-cholesterol was found in the plasma, liver, and feces. For apoA-I overexpression, mice were injected intravenously with apoA-I adenovirus (1011 particles per animal) 3 days before labeled macrophages were injected. ApoA-I overexpression led to significantly higher 3H-cholesterol in plasma, liver, and feces. The amount of 3H-tracer in the liver was 35% higher (P<0.05) and the 3H-tracer excreted into feces over 48 hours was 63% higher (P<0.05) in apoA-I-expressing mice than in control mice. Conclusion--Injection of 3H-cholesterol-labeled macrophage foam cells is a method of measuring reverse cholesterol transport specifically from macrophages to feces in vivo, and apoA-I overexpression promotes macrophage-specific reverse cholesterol transport.
Revised on June 18, 2003
Accepted on June 19, 2003
Overexpression of Apolipoprotein A-I Promotes Reverse Transport of Cholesterol From Macrophages to Feces In Vivo
YuZhen Zhang MD, PhD,
Key words: cholesterol • cholesterol • reverse transport • apolipoproteins • macrophages • atherosclerosis
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