Artery-derived smooth muscle cells from atherosclerosis susceptible pigeons exhibit increased growth potential in vitro and synthesize cell surface heparan sulfate which is deficient in O-sulfate containing disaccharides.

摘要

Vascular smooth muscle cells (SMCs) are vital components of normal arteries. Proliferation of intimal SMCs and/or migration of medial SMCs to the arterial intima contribute to the formation of advanced atherosclerotic lesions. In the present study, smooth muscle cell lines were established in vitro from the thoracic aortas of atherosclerosis-susceptible White Carneau (WC) and resistant Show Racer (SR) pigeons. White Carneau SMCs, grew twice as rapidly (doubling times of 1.92 for WC SMCs versus 2.96 days for SR SMCs) and to higher cell saturation densities in culture (774 cells/mm{dollar}sp2{dollar} for WC, 472 cells/mm{dollar}sp2{dollar} for SR). In addition, growth of both WC and SR SMCs was inhibited by heparin. Heparan sulfate proteoglycans (HSPG) from the cell surface of confluent endothelial cells and SMCs have been identified as regulators of smooth muscle cell (SMC) proliferation. To investigate the contribution of specific disaccharides of HSPG implicated in the regulation of SMC proliferation, the disaccharide composition was determined for HSPG isolated from the surface of confluent SMCs of WC and SR pigeons using anion exchange chromatography. Results indicate that HSPG from WC SMCs have reduced sulfation, primarily due to reductions in O-sulfate containing disaccharides. The sulfation density was also found to be lower in HSPG from WC SMCs resulting from reduced amounts of di- and tri-sulfated disaccharides. Consistent with previously published reports of HSPG structure, oligosaccharide profiles generated following size-exclusion-chromatography of chemically fragmented glycosaminoglycan (GAG) chains isolated from the cell surface of WC and SR SMCs revealed the presence of sulfate-rich and sulfate-poor domains within the GAG chains. These data indicate that cell surface HSPG from WC SMCs are deficient in potential structural determinants of heparan sulfate growth inhibitory activity.