@ Three different families of proteoglycans, which include chondroitin
sulfate (CSPG), dermatan sulfate (DSPG) and heparan sulfate (HSPG), and
hyaluronan accumulate in the extracellular matrix of vascular lesions
and influence vascular cell phenotype. Hyaluronan forms pericellular coats
around arterial smooth muscle cells (ASMCs) and this molecule increases
both inside and outside of cells stimulated to divide. Interference of
hyaluronan binding to hyaluronan receptors on the surface of ASMCs blocks
PDGF induced proliferation and migration. Versican is the major interstitial
CSPG that accumulates in restenotic lesions. Versican is synthesized as
multiple mRNA spliced variants (V0, V1, V3) by ASMCs. Overexpression of
versican by cell mediated gene transfer alters ASMC phenotype and influences
ECM composition in blood vessels subjected to experimental injury. Decorin
is a small DSPG that inhibits TGF-1 activity when overexpressed by ASMC
transduced with decorin cDNA. Transfer of decorin overproducing cells
into injured arteries reduces intimal thickening and stimulates collagen
deposition. Decorin is also synthesized by vascular endothelial cells
during sprouting and tube formation in vitro. The ability of decorin to
stabilize the ECM may be critical to the neovascularization of vascular
lesions. Heparan sulfate proteoglycans partially regulate ASMC migration.
Removal of HSPGs from injured arteries by heparinase treatment is effective
in reducing the mitogenic response induced by bFGF in arterial smooth
muscle cells. Collectively, these studies indicate that not only do proteoglycans
contribute to the mass of restenotic lesions but they also have a dramatic
effect on altering ASMC phenotype.
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