on May 31, 2007
Published online before print May 31, 2007, doi: 10.1161/ATVBAHA.107.146068
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Submitted on November 17, 2006
Accepted on May 14, 2007
In Vivo Reverse Cholesterol Transport From Macrophages Lacking ABCA1 Expression Is Impaired
Ming-Dong Wang ;
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.
* To whom correspondence should be addressed. 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 either 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.
Key words: lipoproteins • HDL • monocyte-derived macrophage
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