Inhibition of Neointima Formation by Anti-Vascular Endothelial Growth Factor and Receptor-1 Peptides in a Balloon-Injured Rat Carotid Artery

Background and Objectives: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen.This study was undertaken to test the hypothesis that the neointima hyperplasia induced by a balloon injuryis inhibited by blocking VEGF and VEGF receptor-1 (VEGFR-1) with anti-VEGF peptides. Materials and Methods:Anti-VEGF RRKRRR peptide (dRK6) and anti-VEGFR-1 peptide (anti-flt-1) were synthesized at Pohang Universityof Science and Technology, Korea. Male Sprague-Dawley rats, weighing 300-350 g, were subcutaneously injected0.5 mg/kg of dRK6 or 0.5 mg/kg of anti-flt-1, dissolved in phosphate buffer solution, 2 days beforeinduction of a carotid balloon-injury, and then daily in the same manner post carotid balloon injury for 2 weeks.Results: Neointima formation was suppressed in both the dRK6 and anti-flt-1 groups compared to that in theuntreated controls at 2 weeks post carotid balloon-injury (neointimal area; control group 0.44±0.09 mm2, dRK6group 0.25±0.05 mm2, anti-flt-1 group 0.19±0.05 mm2, p