Development of a vasoactive biogel

描述(申请人提供)：心血管疾病是美国和其他发达国家的主要死亡原因。心血管疾病的治疗通常包括用人类大隐静脉移植手术绕过闭塞的血管段。在美国，每年大约有1,000,000例主冠状动脉和外周血运重建术使用人类大隐静脉移植物进行。这些手术的一个技术限制是，大隐静脉移植物在收获和准备过程中容易发生血管痉挛。本研究的目的是开发一种预防移植静脉痉挛的多肽类药物。这项研究的假设是，介导血管松弛的磷蛋白的合成肽类似物(热休克相关蛋白-20)可以被优化，并以受控的方式输送，以防止静脉移植物痉挛。这项研究的总体目标是开发一种生物凝胶，它将防止：A)通过预防血管痉挛而防止短期移植物失败；B)通过在收获期间更好地保存移植物而防止长期移植物失败。这种生物凝胶将被开发出来，并使用人体大隐静脉移植物条在体外肌浴中进行生物活性测试。这将导致扩大用于动物试验的生物凝胶的生产。最终产品将在静脉作为旁路管道植入之前直接应用于静脉移植物的表面。

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of death in the United States and other developed countries. The treatment of cardiovascular disease often involves surgically bypassing occluded segments of blood vessels with human saphenous vein grafts. Approximately 1,000,000 aortocoronary and peripheral revascularizations are performed using human saphenous vein grafts each year in the US. A technical limitation of these procedures is that saphenous vein grafts are prone to vasospasm during harvest and preparation. The purpose of this proposal is to develop a peptide based therapeutic agent for the prevention of vein graft spasm. The hypotheses of this investigation is that synthetic peptide analogues of the phosphoprotein that mediates vasorelaxation (heat shock related protein-20) can be optimized and delivered in a controlled manner that will prevent vein graft spasm. The overall goals of this research are to develop a biogel with that will prevent: A) short-term graft failure by preventing vasospasm and B) long-term graft failure by better preservation of the graft during harvest. This biogel will be developed and tested for bioactivity using strips of human saphenous vein graft in a muscle bath ex vivo. This would lead to scaled up production of the biogel for animal trials. The ultimate product would be applied directly to the surface of the vein graft prior to implantation of the vein as a bypass conduit.