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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:442.)
© 2006 American Heart Association, Inc.

Brief Reviews

Apolipoprotein E Recycling

Implications for Dyslipidemia and Atherosclerosis

Joerg Heeren; Ulrike Beisiegel; Thomas Grewal

From the Institute for Biochemistry and Molecular Biology II (J.H., U.B.), Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; and Centre for Immunology (T.G.), St. Vincent’s Hospital, University of New South Wales, Darlinghurst, Sydney, Australia.

Correspondence to Dr Joerg Heeren, IBM II, Molecular Cell Biology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. E-mail heeren{at}uke.uni-hamburg.de

After receptor-mediated endocytosis, the intracellular fate of triglyceride-rich lipoproteins (TRLs) is far more complex than the classical degradation pathway of low-density lipoproteins. Once internalized, TRLs disintegrate in peripheral endosomes, followed by a differential sorting of TRL components. Although core lipids and apolipoprotein B are targeted to lysosomes, the majority of TRL-derived apolipoprotein E (apoE) remains in peripheral recycling endosomes. This pool of TRL-derived apoE is then mobilized by high-density lipoproteins (HDLs) or HDL-derived apoA-I to be recycled back to the plasma membrane, followed by apoE resecretion and the subsequent formation of apoE-containing HDL. The HDL-induced recycling of apoE is accompanied by cholesterol efflux and involves the internalization and targeting of HDL-derived apoA-I to endosomes containing both apoE and cholesterol. These findings point to a yet unknown intracellular link between TRL-derived apoE, cellular cholesterol transport, and HDL metabolism. Recent studies provide first evidence that impaired recycling of TRL-derived apoE4, but not apoE3, is associated with intracellular cholesterol accumulation, which might explain some well-documented effects of apoE4 on HDL metabolism. This review summarizes the current understanding of apoE recycling and its potential role in the regulation of plasma apoE levels in the postprandial state.

Key Words: apolipoprotein E • HDL • endocytosis • cholesterol efflux • triglyceride-rich lipoproteins

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