Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: Clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome
Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: Clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome
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DOI：
10.1016/j.jpeds.2004.10.064
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发表时间：
2005-03-01
影响因子：
5.1
通讯作者：
Lichtenstein, AH
中科院分区：
文献类型：
--
作者：
Gordon, LB;Harten, IA;Lichtenstein, AH
患有Hutehinson-Gilford早衰综合征（HGPS）的儿童死于严重的过早动脉粥样硬化，平均年龄为13岁。虽然已经确定了导致这种“早衰综合征”的LMNA基因缺陷，但加速动脉粥样硬化的生物学机制尚不清楚。我们确定患有HGPS的儿童是否表现出心血管疾病（CVD）风险的已知生物标志物异常。研究设计我们量化了HGPS患儿和同龄对照患儿的血脂、脂蛋白、c反应蛋白（CRP）和脂联素。结果高密度脂蛋白胆固醇（P < 0.0001）和脂联素（P < 0.001）浓度随HGPS患儿年龄的增加而显著降低，而对照组无此现象。这些变量在HGPS患儿中存在正相关（P < 0.0001），而对照组患儿则没有。平均总胆固醇，低密度脂蛋白和高密度脂蛋白胆固醇。甘油三酯和中位CRP水平在HGPS儿童和对照组之间相似（P均为0.05）。结论随着年龄的增长，高密度脂蛋白胆固醇和脂联素的下降可能加速了高血压患者动脉粥样硬化斑块的形成。正常衰老中与心血管疾病风险相关的几个因素（CRP、总胆固醇和低密度脂蛋白胆固醇升高）没有差异，也不太可能影响高血压患者的心血管疾病风险。HDL和脂联素可能是HGPS动脉粥样硬化的重要介质和潜在治疗靶点。
Objectives Children with Hutehinson-Gilford Progeria Syndrome (HGPS) die of severe premature atherosclerosis at an average age of 13 years. Although the LMNA gene defect responsible for this "premature aging syndrome" has been identified, biological mechanisms underlying the accelerated atherosclerosis are unknown. We determined whether children with HGPS demonstrate abnormalities in known biomarkers for cardiovascular disease (CVD) risk.Study design We quantified serum lipids, lipoproteins, C-reactive protein (CRP), and adiponectin in children with HGPS and age-matched control children.Results HDL cholesterol (P < .0001) and adiponectin (P < .001) concentrations decreased significantly with increasing age in HGPS but not in control children. There was a positive correlation between these variables in HGPS (P < .0001) but not control children. Mean total cholesterol, LDL and HDL cholesterol. triglyceride, and median CRP levels were similar between HGPS and control children (all P > .05).Conclusions Declining HDL cholesterol and adiponectin with advancing age may contribute to accelerated atherosclerotic plaque formation in HGPS. Several factors frequently associated with CVD risk in normal aging (elevated CRP, total and LDL cholesterol) showed no difference and are unlikely to influence CVD risk in HGPS. HDL and adiponectin may represent significant mediators and potential therapeutic targets for atherosclerosis in HGPS.