CARDIOVASCULAR EVALUATION OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

纯合子家族性高胆固醇血症的心血管评估

• 批准号: 3779548
• 负责人: J M HOEG
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3779548
• 关键词: antiatherogenic agent; atherosclerosis; cardiovascular disorder chemotherapy; cholesterol; combination chemotherapy; computed axial tomography; coronary disorder; diet therapy; familial hyperlipoproteinemia type II; human subject; human therapy evaluation; human tissue; liver transplantation; longitudinal human study; low density lipoprotein; nutrition related tag; receptor expression; xanthomatosis

Patients homozygous for familial hypercholesterolemia (FH) manifest profound hypercholesterolemia, cutaneous cholesterol deposits termed xanthomas, and cholesterol deposition in a variety of tissues including the eye, tendons, and inside the arterial vessels. These patients experience accelerated atherosclerosis and can manifest symptomatic cardiovascular disease from the ages of 2-30 years, and many die before the age of 20. The cause for the 10 fold increase in total and low density lipoprotein (LDL) cholesterol concentrations is a defect in the ability of the body to extract the cholesterol-rich LDL particles from the circulation via the LDL receptor pathway. A wide variety of mutations in the LDL receptor gene can lead to the loss of the expression of functional LDL receptors on the surface of liver cells. We have previously demonstrated that the degree of LDL receptor dysfunction on cultured skin fibroblasts from these patients highly correlates with the concentrations of LDL cholesterol present in their circulation. We have applied a variety of therapies to reduce the LDL cholesterol concentrations in these patients including diet, combination hypolipidemic drug therapy, portacaval shunting of the liver, plasma exchange, LDL apheresis, and liver transplantation. The degree of coronary artery atherosclerosis and the response to lipid-lowering intervention is variable among patients identified as having this condition. For the past 6 years we have prospectively evaluated the rate of progression of atherosclerosis by both invasive and noninvasive techniques in these patients. We have demonstrated that assessment of the extent and severity of atherosclerosis in these patients can be achieved using Ultrafast Computerized Axial Tomography. No only was this noninvasive test useful in identifying atherosclerotic lesions in patients as young as 3 years of age, it also led to a new concept in atherosclerotic cardiovascular disease risk assessment, the cholesterol- years risk score. These findings in this inborn error in lipoprotein metabolism may have theoretic and practical implications for individuals with more common forms of atherosclerosis.

家族性高胆固醇血症 (FH) 纯合子患者表现 严重的高胆固醇血症，皮肤胆固醇沉积称为 黄色瘤和多种组织中的胆固醇沉积，包括 眼睛、肌腱和动脉血管内部。 这些患者 经历加速动脉粥样硬化并可能出现症状 心血管疾病从2-30岁开始，许多人在此之前就去世了 20岁，总量增加10倍且偏低的原因 密度脂蛋白（LDL）胆固醇浓度是一个缺陷 身体从其中提取富含胆固醇的低密度脂蛋白颗粒的能力 通过 LDL 受体途径进行循环。 种类繁多 LDL受体基因突变可导致表达缺失 肝细胞表面功能性 LDL 受体的变化。 我们有 先前证明LDL受体功能障碍的程度 从这些患者中培养的皮肤成纤维细胞与 其循环中存在的低密度脂蛋白胆固醇浓度。 我们有 应用多种疗法来降低低密度脂蛋白胆固醇 这些患者的浓度，包括饮食、组合 降血脂药物治疗、肝门静脉分流术、血浆 交换、低密度脂蛋白单采术和肝移植。 程度 冠状动脉粥样硬化与降脂反应 被确定患有这种疾病的患者之间的干预措施是可变的 健康）状况。 在过去的 6 年里，我们前瞻性地评估了该比率 侵入性和非侵入性动脉粥样硬化进展的研究 这些患者的技术。 我们已经证明了评估 这些患者动脉粥样硬化的程度和严重程度可以通过 使用超快计算机轴向断层扫描实现。 不仅是这个 无创测试有助于识别动脉粥样硬化病变 患者年仅 3 岁，这也引发了一个新概念 动脉粥样硬化性心血管疾病风险评估、胆固醇 年风险评分。 关于脂蛋白先天性错误的这些发现 新陈代谢可能对个人具有理论和实践意义 与更常见形式的动脉粥样硬化有关。