EFFECT OF LIPIDS ON VASCULAR GRAFT HEALING

脂质对血管移植物愈合的影响

• 批准号: 6527330
• 负责人: Linda M Graham
• 金额: $ 37万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6527330
• 关键词: antioxidants; aorta; cardiovascular transplantation; cell growth regulation; cell membrane; cell migration; dietary lipid; fluidity; fluorocarbon polymers; free radical oxygen; hypercholesterolemia; inhibitor /antagonist; laboratory rabbit; low density lipoprotein; membrane activity; membrane lipids; oxidative stress; polyethylenes; protein structure function; superoxide dismutase; tissue /cell culture; tocopherols; transplant rejection; vascular endothelium; wound healing

DESCRIPTION (Adapted from Applicant's Abstract): Prosthetic grafts are used widely in vascular reconstructive surgery, but their long-term patency is limited, perhaps due to altered cell function caused by oxidized low density lipoprotein (oxLDL). In preliminary studies they have shown that: 1) graft material stimulates monocytic cells to oxidize LDL in vitro, 2) this oxLDL inhibits endothelial cell (EC) migration in vivo. This contributes to the prolonged thrombogenicity and eventual failure of these grafts. The goal of this project is to determine the effect of lipids, especially oxidized lipids, on EC migration on prosthetic grafts. To test their hypothesis, the effect of oxidized lipids on EC migration and the mechanism by which oxLDL inhibits EC migration will be studied. The investigators will first investigate the role of reactive oxygen species (ROS) in oxLDL's inhibition of EC migration. They will characterize the effect of oxLDL on superoxide production by EC, assessing the effect of ROS on EC migration, and determining the ability of antioxidants to restore EC migration in the presence of oxLDL. Since ROS alter membrane fluidity and changes in fluidity affect migration, they will investigate the effect of oxLDL on EC membrane fluidity. They will also evaluate the ability of vitamin E and other antioxidants to prevent changes in membrane fluidity and preserve EC migration. The effect of oxLDL on EC migration on ePTFE graft material in vitro will be studied, and the ability of vitamin E or superoxide dismutase to restore migration determined. Finally, they will study the effect of hypercholesterolemia on EC ingrowth onto prosthetic grafts implanted in rabbits, and assess the ability of vitamin E to preserve endothelial migration. The proposed studies will investigate the role of lipids and lipoproteins, and their oxidatively modified derivatives, in the failure of synthetic vascular grafts to endothelialize. Studies will also address the efficacy of treatment with dietary antioxidants to control lipid oxidation and promote graft healing. This will lead to a better understanding of the role of lipids in the pathophysiology of graft failure. Ultimately, this may lead to methods to promote endothelialization of prosthetic grafts and prolong patency of small-diameter vascular grafts.

描述（改编自申请人的摘要）：使用假体移植物 广泛应用于血管重建手术，但其长期通畅性 有限，可能是由于氧化低密度引起的细胞功能改变 脂蛋白（oxLDL）。他们在初步研究中表明：1）移植 材料刺激单核细胞在体外氧化 LDL，2) 这种 oxLDL 抑制内皮细胞 (EC) 体内迁移。这有助于 这些移植物的血栓形成时间延长并最终失败。目标是 这个项目是确定脂质，特别是氧化脂质的影响， EC 在假体移植物上的迁移。 为了检验他们的假设，氧化脂质对 EC 迁移的影响以及 将研究oxLDL抑制EC迁移的机制。这 研究人员将首先研究活性氧（ROS）的作用 oxLDL 抑制 EC 迁移。他们将描述效果 oxLDL 对 EC 产生超氧化物的影响，评估 ROS 对 EC 的影响 迁移，并确定抗氧化剂恢复 EC 迁移的能力 在 oxLDL 存在的情况下。由于 ROS 会改变膜的流动性并改变 流动性影响迁移，他们将研究oxLDL对EC的影响 膜的流动性。他们还将评估维生素 E 和其他物质的能力 抗氧化剂可防止膜流动性变化并保持 EC 迁移。 oxLDL对体外ePTFE移植材料上EC迁移的影响将是 研究了维生素E或超氧化物歧化酶恢复的能力 迁移确定。最后，他们将研究效果 高胆固醇血症对 EC 向植入假体移植物内生长的影响 兔子，并评估维生素 E 保护内皮迁移的能力。 拟议的研究将调查脂质和脂蛋白的作用，以及 它们的氧化修饰衍生物，在合成血管的失败中 移植物内皮化。研究还将探讨治疗的功效 与膳食抗氧化剂一起控制脂质氧化并促进移植物愈合。 这将有助于更好地了解脂质在 移植失败的病理生理学。最终，这可能会导致方法 促进假体移植物的内皮化并延长移植物的通畅时间 小直径血管移植物。