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Development of Small Diameter Vascular Graft Using Trimeric Peptide

使用三聚肽开发小直径血管移植物

基本信息

批准号：
22890081
负责人：
KUWABARA Fumiaki
金额：
$ 1.96万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Research Activity Start-up
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

项目摘要

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.

背景快速内皮化和防止内膜增生是提高小口径血管移植通畅性的必要条件。使用基于肽阵列的筛选系统，我们确定了肽“CAG（半胱氨酸-丙氨酸-甘氨酸）”，它对内皮细胞具有高亲和力，对平滑肌细胞具有低粘附性。在这项研究中，我们报道了用含有CAG肽的可生物降解聚合物（聚ε-己内酯）构建的新型scvg的体内分析。方法新型SCVG测定0。采用静电纺丝技术制备了直径为7mm、长度为7mm的纤维。采用加CAG组或不加CAG组的scvg对Sprague Dawley大鼠进行颈动脉置换术。分别于植入后1、2、6周进行组织学和生化评价。结果CAG组内皮化比例明显高于C组（CAG vs C: 64）。4±20。0% vs 42%。1±8。第1周P=0。017年,98年。2±2。3%对72%。7±12。9%在2周P=0。001和97。4±4。6% vs 76。7±5。6周P<0。001)。此外，Western blot分析显示，CAG组第1周内皮一氧化氮合酶显著高于C组（CAG vs C: 1）。20±0。37比0。34±0。16日,P = 0。CAG组第6周α-平滑肌肌动蛋白显著低于C组(CAG vs C: 0。89±0。06比1。25±0。22日,P = 0。04)。结论CAG能促进血管内皮快速形成，并有抑制内膜增生的潜力。