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KMID : 0368120070370100475
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Korean Circulation Journal
2007 Volume.37 No. 10 p.475 ~ p.482
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Inhibition of Neointima Formation by Anti-Vascular Endothelial Growth Factor and Receptor-1 Peptides in a Balloon-Injured Rat Carotid ArteryBackground 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 injury is inhibited by blocking VEGF and VEGF receptor-1 (VEGFR-1) with anti-VEGF peptides.
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Lee Jong-Min
Moon Keon-Woong
Yoo Ki-Dong
Her Sung-Ho
Yoon Hee-Jeoung
Jin Seung-Won
Jeon Doo-Soo
Youn Ho-Joong
Chung Wook-Sung
Seung Ki-Bae
Kim Chul-Min
Kim Jae-Hyung
Choi Kyu-Bo
Hong Soon-Jo
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Abstract
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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 injury is 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 University of Science and Technology, Korea. Male Sprague-Dawley rats, weighing 300-350 g, were subcutaneously injected 0.5 mg/kg of dRK6 or 0.5 mg/kg of anti-flt-1, dissolved in phosphate buffer solution, 2 days before induction 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 the untreated controls at 2 weeks post carotid balloon-injury (neointimal area; control group 0.44±0.09 mm2, dRK6 group 0.25±0.05 mm2, anti-flt-1 group 0.19±0.05 mm2, p<0.01). Anti-flt-1 peptide and dRK6 reduced the numbers of proliferative bromodeoxyuridine-labeled cells in the neointima (control group 16.4±10.6%, dRK6 group 3.7±2.1%, anti-flt-1 group 5.9±3.4%, p<0.05). In addition, an inflammatory response, as determined by monocyte chemoattractant protein-1 and interleukin-6 upregulation, which was evident in the controls, was inhibited by both dRK6 and anti-flt-1.
Conclusion：This study suggests anti-vascular endothelial growth factor peptides can reduce the inflammation and neointima formation in balloon injured rat carotid arteries.
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KEYWORD
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Vascular endothelial growth factors, Vascular endothelial growth factor receptor-1, Peptides, Carotid artery injuries
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