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J. Biol. Chem., Vol. 276, Issue 27, 25043-25048, July 6, 2001
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and
From the Department of Pathology and Laboratory Medicine,
University of Cincinnati College of Medicine,
Cincinnati, Ohio 45267-0529
This study showed that synthetic peptides
containing either a single copy or tandem repeat of the receptor
binding domain sequence of apolipoprotein (apo) E, or a peptide
containing its C-terminal heparin binding domain, apoE-(211-243), were
all effective inhibitors of platelet-derived growth factor
(PDGF)-stimulated smooth muscle cell proliferation. In contrast, only
the peptide containing a tandem repeating unit of the receptor binding
domain sequence of apoE, apoE-(141-155)2, was
capable of inhibiting PDGF-directed smooth muscle cell migration.
Peptide containing only a single unit of this sequence,
apoE-(141-155), or the apoE-(211-243) peptide were ineffective in
inhibiting PDGF-directed smooth muscle cell migration. Additional
experiments showed that reductively methylated apoE, which is incapable
of receptor binding yet retains its heparin binding capability, was
equally effective as apoE in inhibiting PDGF-stimulated smooth muscle
cell proliferation. However, reductively methylated apoE was unable to
inhibit smooth muscle cell migration toward PDGF. Additionally, the
receptor binding domain-specific apoE antibody 1D7 also mitigated the
anti-migratory properties of apoE on smooth muscle cells. Finally,
pretreatment of cells with heparinase failed to abolish apoE inhibition
of smooth muscle cell migration. Taken together, these data documented
that apoE inhibition of PDGF-stimulated smooth muscle cell
proliferation is mediated by its binding to heparan sulfate
proteoglycans, while its inhibition of cell migration is mediated
through apoE binding to cell surface receptors.
Received Postdoctoral Fellowship 9920615V from the Southern and
Ohio Valley Consortium of the American Heart Association.
§
To whom correspondence should be addressed: Dept. of Pathology and
Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0529. Tel.: 513-558-9152; Fax:
513-558-2141; E-mail: Huidy@email.uc.edu.
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