Baila-Rueda Lucía, Mateo-Gallego Rocío, Jarauta Estibaliz, de Castro-Orós Isabel, Bea Ana M, Cenarro Ana, Civeira Fernando
Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain.
Biochem Biophys Res Commun. 2014 Apr 11;446(3):731-5. doi: 10.1016/j.bbrc.2013.12.131. Epub 2014 Jan 6.
Familial combined hyperlipidemia (FCHL), the most common inherited disorder of lipid metabolism is characterized by increasing cholesterol synthesis precursors due to hepatic overproduction of cholesterol. The bile acids synthesis pathway has not been previously studied in FCHL. The aim of this work was to study the oxysterol levels which are involved in the bile acids synthesis from cholesterol in FCHL. Clinical parameters and subclinical atherosclerosis were studied in a total of 107 FCHL patients and 126 normolipidemic controls. Non cholesterol sterols (desmosterol and lanosterol) and oxysterols (27-hydroxycholesterol and 24S-hydroxycholesterol) were measured by high performance liquid chromatography tandem mass spectrometry. Desmosterol and lanosterol, markers of cholesterol synthesis, had a positive correlation with BMI and apo B. However, no correlation was found for 24S-hydroxycholesterol and 27-hydroxycholesterol, precursors of bile acids, with these clinical parameters. Only 27-hydroxycholesterol had a positive correlation with apo B, ρ=0.204 (P=0.037). All oxysterol levels were higher in FHCL as compared to normal controls. A total of 59 FCHL subjects (59%) presented values of 24S-hydroxycholesterol above the 95th percentile of this oxysterol in the control population. All oxysterols showed no association with fat mass in contrast with non-cholesterol sterols. FCHL subjects with oxysterol overproduction had less carotid intima media thickness (cIMT), which suggests less atherosclerosis in these subjects. In summary, our data indicate that high oxysterol levels might be good markers of FCHL, unrelated to fat mass, and may exert a protective mechanism for cholesterol accumulation.
家族性混合型高脂血症（FCHL）是最常见的遗传性脂质代谢紊乱疾病，其特征是由于肝脏胆固醇过度生成导致胆固醇合成前体增加。此前尚未对FCHL患者的胆汁酸合成途径进行研究。这项研究的目的是探讨FCHL患者中参与胆固醇合成胆汁酸的氧化甾醇水平。我们对107例FCHL患者和126例血脂正常的对照者进行了临床参数和亚临床动脉粥样硬化的研究。采用高效液相色谱串联质谱法测定非胆固醇甾醇（羊毛甾醇和脱氢胆固醇）和氧化甾醇（27-羟基胆固醇和24S-羟基胆固醇）。胆固醇合成标志物羊毛甾醇和脱氢胆固醇与体重指数（BMI）和载脂蛋白B呈正相关。然而，胆汁酸前体24S-羟基胆固醇和27-羟基胆固醇与这些临床参数之间未发现相关性。只有27-羟基胆固醇与载脂蛋白B呈正相关，ρ=0.204（P=0.037）。与正常对照组相比，FCHL患者的所有氧化甾醇水平均较高。共有59例FCHL受试者（59%）的24S-羟基胆固醇值高于对照组人群该氧化甾醇的第95百分位数。与非胆固醇甾醇不同，所有氧化甾醇均与体脂无关。氧化甾醇过度生成的FCHL受试者的颈动脉内膜中层厚度（cIMT）较小，这表明这些受试者的动脉粥样硬化程度较低。总之，我们的数据表明，高氧化甾醇水平可能是FCHL的良好标志物，与体脂无关，并且可能对胆固醇积累发挥保护作用。
