Abstract
To test the hypothesis that syndecan-1 plays an inhibitory role in the arterial response to injury, carotid arteries of wild-type (C57BL/6) and syndecan-1 null mice were ligated and intimal thickening was analyzed morphometrically. The syndecan-1 null mouse generated thick intimal lesions 28 days after carotid ligation, while the wild-type mouse did not (0.065mm2vs. 0.000mm2, n=5). [3H]-Thymidine incorporation into DNA did not differ between wild-type and syndecan-1 null SMCs in vitro. In contrast, PDGF-BB-stimulated syndecan-1 null SMCs migrated faster than wild type SMCs (by 139%±6.2%, n=3) in the modified Boyden chamber. In addition, PDGF-BB and -DD stimulated shedding of syndecan-1 in vitro (analyzed by dot immunoblot assay), while PDGF-AA, -AB and -CC did not. This suggests that shedding is induced by activation of PDGF receptor-ββ dimers. Also, soluble syndecan-1 ectodomain dose-dependently inhibited PDGF-BB-induced migration of wild-type and null SMCs (EC50=28.8pg/ml). These data suggest that syndecan-1 inhibits neointimal lesion formation after vascular injury by inhibiting SMC migration. Shedding and removal of syndecan-1 may be one mechanism by which PDGF stimulates SMC migration. However, since soluble syndecan-1 ectodomain is inhibitory, further experiments with non-cleavable syndecan-1 mutants are needed to clarify the relative inhibitory effects of membrane bound vs. soluble syndecan-1.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
