Vascular Healing with VEGF-Collagen Binding Chimera

VEGF-胶原蛋白结合嵌合体的血管愈合

• 批准号: 6837758
• 负责人: LUKE Packard BREWSTER
• 金额: $ 5.23万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2006-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837758
• 关键词: angiogenesis; binding sites; cardiovascular disorder chemotherapy; cell migration; cell proliferation; chimeric proteins; collagen; dogs; extracellular matrix; nonhuman therapy evaluation; postdoctoral investigator; protein binding; protein structure function; smooth muscle; vascular endothelial growth factors; vascular endothelium; wound healing

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.

描述（由申请方提供）：快速融合内皮化可减少血小板沉积并减少平滑肌细胞生长，从而最大限度地减少血管介入后的血栓形成和增生。VEGF 121是一种可溶性EC促分裂原和促血管生成素;它将与胶原蛋白结合结构域融合形成独特的嵌合体（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是产生VEGF-CBD，确定其结合I型胶原和暴露的血管壁胶原的能力，并定量地促进体外EC增殖、迁移和血管生成。假设是：VEGF-CBD将在体外促进EC增殖和迁移而不刺激SMC，它将在体外结合胶原蛋白并在体内结合暴露的血管壁胶原蛋白，从而延长生物利用度。目的#2是用内皮损伤模型在体内定量：EC和SMC增殖、管腔再内皮化和肌内膜对VEGF-CBD的反应。假设是VEGF-CBD在体内递送至细胞外基质，将促进汇合的再内皮化，从而使肌内膜增生最小化。VEGFCBD的未来前景可能适用于内膜愈合、表面内皮化和工程组织的毛细血管化。