title: Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide.
abstract: BACKGROUND
  Percutaneous coronary intervention is widely used for the treatment of coronary artery disease; however, significant challenges such as restenosis remain. Key to solving these problems is to inhibit smooth muscle cell activation while enhancing re-endothelialization. Early growth response-1 (Egr-1) is a transcription factor that regulates vascular smooth muscle cell (SMC) proliferation and migration through its control of an array of downstream genes.
  
  
  METHODS
  A "cocktail" of vascular endothelial growth factor (VEGF)-A, VEGF-D and cyclic RGD was tested for its ability to inhibit neointima formation and accelerate re-endothelialization following balloon injury to carotid arteries of rats.
  
  
  RESULTS
  In vitro, the cocktail stimulated endothelial cell growth yet inhibited smooth muscle cell growth. In vivo, cocktail-treated injured arteries exhibited reduced intimal thickening by >50% (P<0.05). It increased both re-endothelialization and endothelial nitric oxide synthase (NOS) expression. Cocktail reduced Egr-1 expression, an effect blocked by the NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) that also prevented cocktail inhibition of neointima inhibition.
  
  
  CONCLUSIONS
  This combination may potentially be useful for the treatment of restenosis with concomitant stimulation of revascularization.
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia; Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Lucinda S
authors.initials: LS
authors.lastname: McRobb
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: l.khachigian@unsw.edu.au.
authors.forename: Levon M
authors.initials: LM
authors.lastname: Khachigian
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000379:methods; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid
keywords: Egr-1; Hyperplasia; Intimal thickening; Vascular endothelial cells; Vascular smooth muscle cells