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Originally published In Press as doi:10.1074/jbc.M200219200 on May 28, 2002

J. Biol. Chem., Vol. 277, Issue 33, 29477-29483, August 16, 2002
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Regulation of Macrophage ApoE Expression and Processing by Extracellular Matrix*

Yuwei Zhao, Lili Yue, DeSheng Gu, and Theodore MazzoneDagger

From the Departments of Medicine and Biochemistry, Rush Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612

Macrophage-derived apoE in the vessel wall has important effects on atherogenesis in vivo, making it important to understand factors that regulate its expression. Vessel wall macrophages are embedded in an extracellular matrix produced largely by arterial smooth muscle cells and endothelial cells. In this series of studies, we evaluated the influence of extracellular matrix on macrophage apoE expression. Subendothelial matrix, fibronectin, or collagen I stimulated macrophage apoE gene expression and apoE synthesis. Adhesion of macrophages to a polylysine substrate had no effect. An increase in apoE synthesis after plating on fibronectin could be observed by 2 h and was inhibited by blocking antibodies to the alpha 5beta 1 integrin receptor for fibronectin. Fibronectin also regulated the post-translational processing of newly synthesized macrophage apoE by inhibiting its degradation. The increment in apoE resulting from suppressed degradation was retained in the cell-fibronectin monolayer in a pool that was resistant to release by exogenous high density lipoprotein subfraction 3. These observations establish a new pathway for the regulation of macrophage apoE expression in the vessel wall. The composition of the extracellular matrix changes after vessel wall injury and in response to locally produced cytokines and growth factors. The evolving composition of this matrix will, therefore, be important for regulating apoE expression and processing by vessel wall macrophages.


* This work was supported by Grants HL 59489 and HL 39653 from the National Institutes of Health (to T. M.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Rush Medical Center, 1653 W. Congress Pkwy, Chicago, IL 60612. Tel.: 312-942-8231; Fax: 312-942-8233; E-mail: tmazzone@rush.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.