Development of Small Diameter Vascular Graft Using Trimeric Peptide

背景快速内皮化和防止内膜增生是提高小口径血管移植物通畅性的关键。利用基于肽阵列的筛选系统，我们鉴定出与内皮细胞具有高亲和力、对血管细胞具有低粘附性的多肽“CAG(半胱氨酸-丙氨酸-甘氨酸)”。在这项研究中，我们报告了一种由含有CAG肽的可生物降解聚合物(聚ε-己内酯)构建的新型SCVGs的体内分析。方法新型SCVG，测量0。直径7 mm，长度7 mm，采用静电纺丝技术制备。SD大鼠颈动脉置换术分为CAG组(CAG组)和非CAG组(C组)。分别于植入后1、2、6周取材进行组织学和生化检测。结果CAG组血管内皮化率明显高于C组(CAG vs C：)。4±20.0%对42%。1周时1±8.9%，P=0。017，98。2±2.3%对72%。2周时7±12.9%，P=0。001和97。4±4.6%对76%。6周时为7±5.4%。001)。免疫印迹分析显示，1周时CAG组内皮型一氧化氮合酶活性显著高于C组(CAG vs C组：1.20±0。37比0。34±0。16，P=0。6周时CAG组α-平滑肌肌动蛋白的表达显著低于C组(CAG vs C：0。89±0。06比1.25±0。22，P=0。04)。结论带CAG的移植物具有促进血管内皮化和抑制内膜增生的作用。

Background 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. In this study, we report an in vivo analysis of the novel SCVGs that were constructed with a biodegradable polymer(poly-ε-caprolactone) containing CAG peptide. Methods 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). Histological and biochemical assessments were performed at 1, 2 and 6 weeks after implantation. Results The ratio of endothelialization was significantly higher in group CAG compared to group C(CAG vs C : 64. 4±20. 0% vs 42. 1±8. 9% at 1 week P=0. 017, 98. 2±2. 3% vs 72. 7±12. 9% at 2 weeks P=0. 001, and 97. 4±4. 6% vs 76. 7±5. 4% at 6 weeks P<0. 001). Additionally, Western blot analysis showed that the endothelial nitric oxide synthase at 1 week of group CAG was significantly higher than that of group C(CAG vs C : 1. 20±0. 37 vs 0. 34±0. 16, P=0. 013), and thatα-smooth muscle actin at 6 weeks in group CAG was significantly lower than that of group C(CAG vs C : 0. 89±0. 06 vs 1. 25±0. 22, P=0. 04). Conclusions The graft with CAG promoted rapid endothelialization and potential to inhibition of intimal hyperplasia.