Vascular Healing with VEGF-Collagen Binding Chimera

描述（由申请人提供）：快速融合内皮化减少血小板沉积，减少平滑肌细胞生长，减少血管干预后血栓形成和增生。VEGF121是可溶性EC有丝分裂原和血管原；它将融合到胶原结合域形成独特的嵌合体（VEGF-CBD）。一旦定位于胶原蛋白，它应该通过几种机制促进内皮化。目的1是创造VEGF-CBD，确定其与I型胶原蛋白和暴露的血管壁胶原蛋白结合的能力，并定量促进体外EC增殖、迁移和血管生成。假设是：VEGF-CBD在体外不刺激SMCs的情况下促进EC增殖和迁移，在体外与胶原结合，在体内与暴露的血管壁胶原结合，延长生物利用度。目的2是在内皮损伤模型中量化EC和SMC的增殖、腔内再内皮化和对VEGF-CBD的肌内膜反应。假设VEGF-CBD在体内传递到细胞外基质，将促进融合再内皮化，从而最大限度地减少肌内膜增生。VEGFCBD的未来前景可能应用于内膜愈合、表面内皮化和工程组织的毛细血管化。

DESCRIPTION (provided by applicant): Rapid confluent endothelialization decreases platelet deposition and lessens smooth muscle cell growth, minimizing thrombosis and hyperplasia after vascular interventions. VEGF121 is a soluble EC mitogen and angiogen; it will be fused to a collagen-binding domain to form a unique chimera (VEGF-CBD). Once localized to collagen, it should promote endothelialization through several mechanisms. Aim #1 is to create VEGF-CBD, define its ability to bind to collagen type I and to exposed vessel wall collagen, and to promote in vitro EC proliferation, migration, and angiogenesis quantitatively. The hypotheses are: that VEGF-CBD will promote EC proliferation and migration in vitro without stimulating SMCs, that it will bind to collagen in vitro and to exposed vessel wall collagen in vivo prolonging bioavailability. Aim #2 is to quantify in vivo: EC and SMC proliferation, luminal re-endothelializaton, and myointimal response to VEGF-CBD with an endothelial injury model. The hypothesis is that VEGF-CBD, delivered in vivo to the extracellular matrix, will promote confluent re-endothelialization that minimizes myointimal hyperplasia. Future promise for VEGFCBD may apply to intimal healing, surface endothelialization, and capillarization of and engineered tissues.