Inhibition of intimal thickening after vascular injury with a cocktail of vascular endothelial growth factor and cyclic Arg-Gly-Asp peptide

Yue Li, Lucinda S. McRobb, Levon M. Khachigian*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

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-NG-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.

Original languageEnglish
Pages (from-to)185-191
Number of pages7
JournalInternational Journal of Cardiology
Volume220
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Vascular smooth muscle cells
  • Vascular endothelial cells
  • Egr-1
  • Intimal thickening
  • Hyperplasia

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