Development of a method to improve ischemia due to angiogenesis introducing from bypass grafts activating autologous bFGF at CABG

碱性成纤维细胞生长因子(碱性成纤维细胞生长因子)是最强的血管生成因子之一，可影响参与伤口愈合的所有细胞类型。碱性成纤维细胞生长因子在调节细胞增殖和有丝分裂中起着重要作用，因此分布广泛。缺血心脏侧支循环的形成是由bFGFF等血管生成因子诱导的，我们假设搭载自体血管生成因子的旁路移植可以诱导血管生成，小毛细血管作为侧支循环。组织碎片(Tf-)移植物从植入后不久起就具有丰富的血管生成活性，当用于冠状动脉位置的小直径血管假体时，它可能会促进侧支循环形成到缺血区。我们研制了一种转移因子移植物，并观察了愈合过程，包括血管生成和内皮化。在一项犬研究中，移植后5天内皮细胞增殖活跃，毛细血管形成。7天时内膜组织完全增厚。这些结果表明，内源性碱性成纤维细胞生长因子在血管假体的血管生成中起重要作用，而血栓和感染可能会产生负面影响。如果我们能够拥有良好的基础小直径织物假体，具有良好的操控性和良好的抗血栓性能，那么具有活跃血管生成的移植物用于冠状动脉血运重建是可能的。

Basic fibroblast growth factor (bFGF) is one of the strongest angiogenic agent, and affects all cell types involved in wound healing. The distribution of bFGF is widespread, because it plays an important role in regulating cell proliferation and mitosis. Collateral formation in ischemic heart is induced by angiogenic factors including bFGF.We hypothesized that bypass grafts with autologous angiogenic factors could induce angiogenesis and small capillaries will work as collateral circulation. Tissue-fragmented (TF-) grafts are rich of angiogenic activity, from shortly after implantation and its ability may work for collateral formation to the ischemic area when it is used for a small diameter vascular prosthesis in the coronary artery position. We developed a TF-graft and observed the healing process including angiogenesis and endothelialization. Proliferation of endothelial cells with capillary formation were active in the graft wall 5 days after implantation in a canine study. The full thickness of the intima was organized at 7 days. These results demonstrated that endogenous bFGF is important for angiogenesis in vascular prostheses, whereas thrombus and infection might have a negative effect. It might be possible to have grafts with active angiogenesis for coronary revascularization, if we could have fine basic small-diameter fabric prosthesis with good handling characteristics, excellent antithrombogehicity.