RETENTION OF LIPOPROTEIN BY LESION-PRONE AORTA

与动脉粥样硬化相关的疾病是美国人死亡的主要原因。 各州。当输血时，患此类疾病的风险就会增加。 低密度脂蛋白(LDL)水平升高。然而，众所周知 动脉粥样硬化的风险因素只能解释大约一半的风险， 表明当地因素在国家层面上的重要性。 动脉。拟议的研究检验了一种假设，即早期事件发生在 兔动脉粥样硬化的形成是大量的 动脉中未降解的脂蛋白，其形式不容易交换 用电浆。长时间保留大量的低密度脂蛋白和β- 极低密度脂蛋白是胆固醇喂养兔血浆中的一种重要脂蛋白，在 动脉可能允许这些脂蛋白转化形成(S) 它可以将单核细胞募集到动脉中，促进血管内皮细胞的转化 组织巨噬细胞转化为泡沫细胞。这些研究利用了 高脂饮食兔早期动脉粥样硬化的研究 可预测的主动脉部位，而邻近的主动脉部位抵抗 动脉硬化。低密度脂蛋白在体内蓄积和滞留的比较 易病变和邻近病变抵抗的主动脉在不同的时间 胆固醇喂养应该提供一种灵敏的手段来确定 低密度脂蛋白的积聚和滞留在动脉粥样硬化的形成中起着重要作用。至 进一步研究这一假说，积累和保留 易病变和抗病变的主动脉内未降解的低密度脂蛋白将 当动脉粥样硬化因以下原因引起的主动脉损伤而加重时进行检查 气囊导管，这是有理论基础的建议 低密度脂蛋白在动脉内的滞留可能增加。关于主动脉的数据 未降解的低密度脂蛋白和主动脉低密度脂蛋白降解产物的积累 在注射放射性标记低密度脂蛋白后，将在不同的时间收集。 通过对这些数据应用复杂的数学计算机建模，它 将有可能确定低密度脂蛋白的浓度和保留时间 在大动脉内。还可以确定相关角色 低密度脂蛋白的进入、流出、降解和隔离的速度 在主动脉内，在决定未降解的蓄积和滞留方面发挥作用 主动脉内的低密度脂蛋白。作为比较，低密度脂蛋白在主动脉中的滞留时间将 通过独立的方法从上述示踪剂数据中确定。 低密度脂蛋白的封存也将通过生物化学方法解决。这个 将以类似的方式研究β-极低密度脂蛋白与动脉的相互作用。 这些研究应该提供对以下过程的洞察 动脉粥样硬化在兔身上发生，并提出了可能的途径 人类的动脉粥样硬化可能会被抑制或预防。

Diseases related to atherosclerosis are major causes of death in the United States. The risk of suffering from such diseases is increased when blood levels of low density lipoprotein (LDL) are elevated. However, all known risk factors for atherosclerosis can explain only about half of the risk, suggesting the importance of local factors acting at the level of the artery. The proposed studies examine the hypothesis that an early event in atherogenesis in rabbits is prolonged retention of large amounts of undegraded lipoprotein in artery in a form that does not readily exchange with the plasma. Prolonged retention of large amounts of LDL, and beta- VLDL, a prominent lipoprotein in plasma of cholesterol-fed rabbits, in artery could potentially allow conversion of these lipoproteins to form(s) which could recruit monocytes into artery and facilitate transformation of tissue macrophages into foam cells. These studies take advantage of the fact that cholesterol-fed rabbits develop early atherosclerosis in predictable aortic sites whereas adjacent aortic sites are resistant to atherosclerosis. Comparison of accumulation and retention of LDL within lesion-prone and adjacent lesion-resistant aorta at different times of cholesterol feeding should provide a sensitive means of determining whether accumulation and retention of LDL plays a role in atherogenesis. To further investigate this hypothesis, accumulation and retention of undegraded LDL within lesion-prone and lesion-resistant aorta will be examined when atherosclerosis is exacerbated by aortic injury produced by balloon catheter, for which there is a theoretical basis to suggest that sequestration of LDL within artery might be increased. Data for aortic accumulation of undegraded LDL and products of aortic degradation of LDL will be collected for different times after injection of radiolabeled LDL. By applying sophisticated mathematical computer modeling to those data, it will be possible to determine concentrations and retention times of LDL within aorta. It will also be possible to determine the relative roles that rates of entry, efflux, and degradation, and sequestration of LDL within aorta, play in determining accumulation and retention of undegraded LDL within aorta. For comparison, retention times of LDL within aorta will be determined from the above tracer data by an independent method. Sequestration of LDL will also be addressed by biochemical methods. The interaction of beta-VLDL with artery will be studied in a similar manner. These studies should provide insight into processes by which atherosclerosis develops in rabbits, and suggest possible ways that atherosclerosis in humans might be inhibited or prevented.