Collagen suppresses the proliferative phenotype of allylamine-injured vascular smooth muscle cells

Atherosclerosis. 2002 Jun;162(2):289-97. doi: 10.1016/s0021-9150(01)00718-3.


Repeated cycles of oxidative injury by allylamine induce proliferative rat vascular smooth muscle cell (vSMC) phenotypes characterized by enhanced secretion of osteopontin (OPN). The present study was designed to evaluate the role of extracellular matrix (ECM) interactions in the induction of proliferative phenotypes in this model of oxidant injury. Because OPN is involved in ECM/integrin signaling, and may participate in proliferative control, the proliferation profiles of control and allylamine vSMCs seeded on different matrices were compared. Allylamine cells exhibited a proliferative advantage over controls when seeded on plastic, Pronectin, or fibronectin, but not type I collagen. Addition of GRGDS peptide selectively enhanced [3H]-thymidine incorporation in allylamine vSMCs, while anti-OPN antibodies nullified their proliferative advantage. Allylamine cells exhibited altered expression of alpha1, alpha5 and beta3 integrin subunits and enhanced downstream integrin-coupled increases in focal adhesion kinase, AP-1 and NF-kappaB binding activity. Inhibition of NF-kappaB by pyrrolidine dithiocarbamate selectively compromised proliferation of allylamine vSMCs, while seeding on a non-permissive collagen matrix ablated enhancement of NF-kappaB inducibility. These results implicate ECM interactions in the deregulation of vSMC proliferation following repeated cycles of oxidative chemical injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allylamine / poisoning*
  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cells, Cultured
  • Collagen Type I / pharmacology*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Integrins / physiology
  • Male
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / pathology*
  • Muscle, Smooth, Vascular / physiopathology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Oligopeptides / pharmacology
  • Osteopontin
  • Phenotype
  • Protein-Tyrosine Kinases / metabolism
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins / physiology
  • Thiocarbamates / pharmacology
  • Thymidine / metabolism
  • Transcription Factor AP-1 / metabolism


  • Collagen Type I
  • Integrins
  • NF-kappa B
  • Oligopeptides
  • Pyrrolidines
  • Sialoglycoproteins
  • Spp1 protein, rat
  • Thiocarbamates
  • Transcription Factor AP-1
  • Osteopontin
  • pyrrolidine dithiocarbamic acid
  • Allylamine
  • glycyl-arginyl-glycyl-aspartyl-serine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Ptk2 protein, rat
  • Thymidine