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J. Biol. Chem., Vol. 277, Issue 33, 29477-29483, August 16, 2002
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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
Regulation of Macrophage ApoE Expression and Processing by
Extracellular Matrix*
5
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.
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.
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