Cell specific effects of glycosaminoglycans on the attachment and proliferation of vascular wall components.

Capillary formation has been correlated with changes in basement membrane-associated glycosaminoglycans (GAGs). During capillary growth when endothelial cells (EC) undergo extensive proliferation and migration and pericytes are scarce, hyaluronic acid (HA) levels are elevated. Upon capillary maturation when EC migration and proliferation cease and pericytes appear, the dominant GAG is heparan sulfate (HS). To investigate the potential role of GAGs in the angiogenic process, we studied the effect of HA, heparin, chondroitin sulfate, and dermatan sulfate on the attachment and proliferation of vascular wall cells in vitro. Cell attachment was studied by determining the number of cells attached to GAG-treated substrates. Whereas HA inhibited the attachment of both pericytes and smooth muscle cells (SMC) by nearly 80% after 8 hr, it enhanced capillary EC attachment by more than 30%. Retinal pigment epithelial cells and dermal fibroblasts were employed as controls and none of the GAGs examined significantly altered the attachment of these cells. The effect of GAGs on cell proliferation was determined by the addition of soluble GAGs to cells cultured for the time required for three population doublings. Heparin addition resulted in a dose-dependent inhibition of both pericyte and SMC proliferation with maximal inhibition of 50% at 100 micrograms/ml, whereas this concentration of heparin moderately enhanced capillary EC proliferation. These effects were not observed for any other cell type or with any other GAG and indicate that GAGs have cell-specific effects on the attachment and proliferation of cells of the vascular wall.