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.
Thesaurus Terms: biotherapeutic agent, blood vessel transplantation, drug design /synthesis /production, gel, heat shock protein, synthetic peptide, vasoactive agent, vasospasm, vein biomaterial development /preparation, dosage forms, slow release drug, transplant rejection animal tissue, human tissue
