Syndecan-1: an inhibitor of arterial smooth muscle cell growth and intimal hyperplasia.
OBJECTIVE
Arterial injury induces smooth muscle cell (SMC) proliferation, migration, and intimal accumulation of cells and extracellular matrix. These processes are regulated by the administration of the glycosaminoglycans heparin and heparan sulfate, but little is known about the role of endogenous heparan sulfate proteoglycans in the vessel wall. We investigated the response to carotid injury of syndecan-1-null mice to assess the function of one of a conserved family of transmembrane heparan and chondroitin sulfate proteoglycans.


RESULTS
Syndecan-1-null mice developed a large neointimal lesion after injury, whereas wild-type mice made little or none. This was accompanied by a significant increase in both medial and intimal SMC replication. Cultured syndecan-1-null SMCs showed a significant increase in proliferation in response to PDGF-BB, thrombin, FGF2, EGF, and serum. In response to thrombin, PDGF-BB, and serum syndecan-1-null SMCs expressed more PDGF-B chain message than did wild-type SMCs. Downregulation of PDGF-BB or PDGFRbeta inhibited thrombin-, PDGF-BB-, and serum-induced DNA synthesis in syndecan-1-null SMCs.


CONCLUSIONS
These results suggest the possibility that syndecan-1 may limit intimal thickening in injured arteries by suppressing SMC activation through inhibition of SMC PDGF-B chain expression and PDGFRbeta activation.
Fukai
Nozomi
N
Department of Surgery and Center for Cardiovascular Biology, University of Washington, Seattle, WA 98195-6410, USA.
Kenagy
Richard D
RD
Chen
Lihua
L
Gao
Lu
L
Daum
Guenter
G
Clowes
Alexander W
AW
D000818:Animals; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004261:DNA Replication; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006965:Hyperplasia; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015398:Signal Transduction; D053668:Syndecan-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D004815:Epidermal Growth Factor; D020797:Receptor, Platelet-Derived Growth Factor beta; D013917:Thrombin