Syndecan-1: an inhibitor of arterial smooth muscle cell growth and intimal hyperplasia

Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1356-62. doi: 10.1161/ATVBAHA.109.190132. Epub 2009 Jul 10.

Abstract

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.

Methods and 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin
  • Carotid Artery Injuries / metabolism*
  • Carotid Artery Injuries / pathology
  • Carotid Artery, Common / metabolism
  • Carotid Artery, Common / pathology
  • Cell Movement
  • Cell Proliferation*
  • Cells, Cultured
  • DNA Replication
  • Disease Models, Animal
  • Epidermal Growth Factor / metabolism
  • Fibroblast Growth Factor 2 / metabolism
  • Hyperplasia
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Platelet-Derived Growth Factor / metabolism
  • Proto-Oncogene Proteins c-sis / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Signal Transduction
  • Syndecan-1 / deficiency
  • Syndecan-1 / genetics
  • Syndecan-1 / metabolism*
  • Thrombin / metabolism
  • Time Factors
  • Tunica Intima / metabolism*
  • Tunica Intima / pathology

Substances

  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Sdc1 protein, mouse
  • Syndecan-1
  • Fibroblast Growth Factor 2
  • Becaplermin
  • Epidermal Growth Factor
  • Receptor, Platelet-Derived Growth Factor beta
  • Thrombin