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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1837.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

In Vivo Reverse Cholesterol Transport From Macrophages Lacking ABCA1 Expression Is Impaired

Ming-Dong Wang; Vivian Franklin; Yves L. Marcel

From the Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Departments of Biochemistry, Microbiology, and Immunology, and of Pathology and Laboratory Medicine, University of Ottawa, Ontario, Canada.

Correspondence to Y. Marcel, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada. E-mail ylmarcel{at}ottawaheart.ca

Background— ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of reverse cholesterol transport (RCT) in vivo. Macrophage specific abca1 inactivation or overexpression, respectively, accelerated or suppressed the development of atherosclerosis in mouse models. However, it is yet to be established that the ABCA1 effect is related to specific changes in RCT from the macrophages in vivo.

Methods And Results— Bone marrow–derived macrophages from abca1^–/– or abca1^+/– mice were labeled with ³H-cholesterol-AcLDL or ³H-cholesterol-LDL and injected into abca1^+/+ abca1^+/– or abca1^–/– mice. When injected into abca1^+/+ mice, return of ³H-cholesterol from labeled abca1^–/– macrophages to serum, liver, bile, and feces was reduced by 50% (P=0.01) compared with control. When labeled wild-type macrophages were injected into abca1^–/– mice, as compared with wild-type mice, the return of ³H-cholesterol to serum, liver, bile, and feces was also reduced.

Conclusions— ABCA1 expression in macrophages contributes significantly to in vivo macrophage RCT. The important residual RCT observed from abca1^–/– macrophages highlight the functionality of transporters that efflux to HDL.

ATP-binding cassette transporter A1 (ABCA1) is a key mediator of cholesterol efflux to apoA-I in cholesterol loaded macrophages, a first step of reverse cholesterol transport (RCT) in vivo. Here we demonstrate that abca1 inactivation in macrophages significantly impairs in vivo RCT.

Key Words: lipoproteins • HDL • monocyte-derived macrophage

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