Inhibition of restenosis formation without compromising reendothelialization as a potential solution to thrombosis following angioplasty?

Endothelium. Jan-Feb 2008;15(1):85-92. doi: 10.1080/10623320802092484.

Abstract

Stent thrombosis remains an important problem after the implantation of different stent types. A potential solution to this problem may be vasoactive agents with dual effects on different cell types like C-type natriuretic peptide (CNP). Therefore, in vitro and in vivo effects of CNP were investigated in a porcine restenotic model. Gene transfer of CNP in cultures of porcine vascular cells revealed up to 30% reduction of growth of smooth muscle cells (p<.05), but no suppression of endothelial growth using CNP. Applied in vivo, angiography revealed a trend of reduced restenosis formation in balloon-injured porcine arteries treated with CNP gene or beta-galactosidase (beta-Gal) control gene after three months (2.59 +/- 2.04-fold reduction, p = n.s.). Histologically, morphometry revealed significantly reduced neointima formation after treatment with CNP plasmid (7.26 +/- 1.44-fold reduction, p < .05). Evans blue staining demonstrated complete endothelial repair already 3 weeks after intervention using CNP. Transfer of CNP gene resulted in a significant inhibition of neointima formation without compromising endothelial repair. Therefore, use of the CNP gene may offer a solution to suppress restenosis formation while preventing subacute or late thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiography
  • Angioplasty, Balloon / adverse effects*
  • Animals
  • Arteries / cytology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Coloring Agents / metabolism
  • Constriction, Pathologic
  • DNA / genetics
  • Disease Models, Animal
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / physiopathology
  • Evans Blue / metabolism
  • Gene Expression
  • Gene Transfer Techniques*
  • Immunohistochemistry
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Natriuretic Peptide, C-Type / administration & dosage*
  • Natriuretic Peptide, C-Type / genetics*
  • Swine
  • Thrombosis / prevention & control*
  • Time Factors
  • Transfection
  • Tunica Intima / drug effects

Substances

  • Coloring Agents
  • Natriuretic Peptide, C-Type
  • Evans Blue
  • DNA