Novel Small-Caliber Vascular Grafts With Trimeric Peptide for Acceleration of Endothelialization

Abstract

Both rapid endothelialization and the prevention of intimal hyperplasia are essential to improve the patency of small-caliber vascular grafts (SCVGs). Using the peptide array based screening system, we identified the peptide CAG (cysteine-alanine-glycine), which has a high affinity for endothelial cells and a low adhesive property for smooth muscle cells (SMCs). In this article, we report an in vivo analysis of novel vascular grafts that were constructed with a biodegradable polymer (poly-ε-caprolactone [PCL]) containing CAG peptide. The novel SCVG, which measured 0.7 mm in diameter and 7 mm in length, was fabricated using the electrospinning technique. Carotid arterial replacement was performed on Sprague-Dawley rats using SCVGs with (group CAG) or without CAG (group C). Histologic and biochemical assessments were performed at 1, 2, and 6 weeks after implantation. The ratio of endothelialization was significantly higher in group CAG compared with group C (CAG versus C, 64.4±20.0% versus 42.1±8.9% at 1 week; p=0.017; 98.2±2.3% versus 72.7±12.9% at 2 weeks; p=0.001; and 97.4±4.6% versus 76.7±5.4% at 6 weeks; p<0.001). Additionally, Western blot analysis showed that the level of endothelial nitric oxide synthase (eNOS) at 1 week in group CAG was significantly higher than that in group C (CAG versus C, 1.20±0.37 versus 0.34±0.16; p=0.013), and that α-smooth muscle actin (ASMA) at 6 weeks in group CAG was significantly lower than that in group C (CAG versus C, 0.89±0.06 versus 1.25±0.22; p=0.04). The graft with CAG promoted rapid endothelialization and the potential for inhibition of intimal hyperplasia.