EFFECT OF LIPIDS ON VASCULAR GRAFT HEALING

描述(摘自申请者摘要)：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)。在初步研究中，他们表明：1)嫁接 材料在体外刺激单核细胞氧化低密度脂蛋白，2)这种氧化低密度脂蛋白 抑制内皮细胞(EC)在体内的迁移。这有助于 长时间的血栓形成和这些移植物的最终失败。的目标是 这个项目是为了确定脂质，特别是氧化脂质的影响， EC在假体移植物上的迁移。 为了验证他们的假设，氧化脂质对EC迁移的影响以及 氧化低密度脂蛋白抑制EC迁移的机制将被研究。这个 调查人员将首先调查活性氧物种(ROS)的作用 OxLDL对EC迁移的抑制作用。他们将描述 氧化低密度脂蛋白对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改变了膜的流动性并改变了 流动性影响迁移，他们将调查oxLDL对EC的影响 膜流动性。他们还将评估维生素E和其他 抗氧化剂，以防止膜流动性的变化和保护EC的迁移。 氧化低密度脂蛋白对内皮细胞在ePTFE移植材料上迁移的影响 以及维生素E或超氧化物歧化酶恢复的能力 已确定迁移。最后，他们将研究 EC植入假体后的高胆固醇血症 并评估维生素E保存内皮细胞迁移的能力。 拟议的研究将调查脂类和脂蛋白的作用，以及 其氧化修饰的衍生物，在人造血管的失败 移植物内皮化。研究还将涉及治疗的效果 添加抗氧化剂，控制脂肪氧化，促进移植物愈合。 这将使我们更好地理解脂质在体内的作用。 移植失败的病理生理学。最终，这可能会导致方法 促进人工血管内皮化，延长血管通畅率 小直径血管移植物。

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.