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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:143.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Scavenger Receptor Class B Type I Mediates the Selective Uptake of High-Density Lipoprotein–Associated Cholesteryl Ester by the Liver in Mice

May Brundert; Anne Ewert; Joerg Heeren; Barbara Behrendt; Rajasekhar Ramakrishnan; Heiner Greten; Martin Merkel; Franz Rinninger

From University Hospital Hamburg-Eppendorf (M.B., A.E., J.H., B.B., H.G., M.M., F.R.), Hamburg, Germany; and the College of Physicians and Surgeons of Columbia University (R.R.), New York, NY.

Correspondence to Dr Franz Rinninger, University Hospital Hamburg-Eppendorf, Department of Medicine, Martinistrasse 52, 20246 Hamburg, Germany. E-mail Rinninger{at}uke.uni-hamburg.de

Objective— High-density lipoprotein (HDL) cholesteryl esters (CE) are taken up by liver and adrenals selectively, ie, independent from particle internalization. Class B type I scavenger receptor (SR-BI) mediates this uptake in vitro. The role of SR-BI in HDL metabolism was explored in mice.

Methods and Results— Mice with a mutation in the SR-BI gene (SR-BI KO) and wild-type (WT) littermates were used. Mutants had increased HDL cholesterol. HDL was labeled with ¹²⁵I (protein) and [³H] (CE). After HDL injection, blood samples were drawn and finally the mice were euthanized. In WT, the plasma decay of HDL-associated [³H] is faster compared with ¹²⁵I and this represents whole-body selective CE uptake. In SR-BI KO, the decay of both tracers is similar, yielding no selective CE removal. In WT liver and adrenals, uptake of [³H] is higher than ¹²⁵I, showing selective uptake. In SR-BI KO, liver uptake of [³H] and ¹²⁵I are similar, proposing no selective HDL CE uptake. In SR-BI KO adrenals, selective uptake is reduced; however, even in the absence of SR-BI, this uptake is detected using WT-HDL.

Conclusions— SR-BI mediates selective uptake of HDL CE by the liver. In adrenals, an alternative mechanism or mechanisms can play a role in selective CE uptake.

In mice with a targeted mutation in the SR-BI gene (knockout), no HDL-selective CE uptake is detected in the liver. This result is contrast to results found with wild-type animals. SR-BI has a physiological role in selective HDL CE uptake in vivo.

Key Words: HDL • SR-BI • cholesterol • liver • receptor

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