目的:本研究旨在利用先进的脂质组学平台,通过研究家族性高胆固醇血症(FH)患者血脂代谢网络的定量和定性异常,确定精确的生物标志物并制定有针对性的治疗策略,以预防这些患者的过早动脉粥样硬化性心血管疾病。
方法:研究人群包括18个纯合(HoFH),18例杂合子(HeFH)FH患者,和20个健康对照。胆固醇氧化产物(氧固醇,使用气相色谱-质谱法确定COP)和主要脂质类别。结果表示为脂质类别的总脂肪物质的百分比和氧固醇的总COP的百分比。还进行了主成分分析(PCA),强调所研究的参数和所研究的群体之间的相关性。
结果:与对照组相比,患者(HoFH和HeFH)显示出更低的游离脂肪酸(FFA)含量和更高的三酰甘油(TAG)值。与HeFH和对照相比,HoFH显示出较低的单酰基甘油(P<0.01)和较高的游离胆固醇(FC)(P<0.05)。总含量为1.96~4.25mg/dL,从2.27到4.05mg/dL,健康对照组为0.79至4.12mg/dL,HoFH和HeFH组,分别,患者和对照组之间没有显着差异。总的来说,7α-羟基胆固醇(7α-HC)高于其他COP。然而,三个研究组之间没有发现显著差异.此外,在7α-HC和7-酮胆固醇(7-KC)之间观察到相反的趋势。此外,当PCA进行时,前两台PC解释了总方差的92.13%,其中PC1描述了53.94%的方差,主要与标签相关,二酰基甘油(DAG),7-KC另一方面,PC2主要与FFA相关,FC和酯化甾醇(E-STE)。
结论:结论:标签的异常水平,DAG和7-KC与HeFH相关,而HoFH与E-STE异常量相关。
OBJECTIVE: This study aimed to identify precise biomarkers and develop targeted therapeutic strategies for preventing premature atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia (FH) by investigating the quantitative and qualitative abnormalities in the metabolic network of lipids in these patients using an advanced lipidomics platform.
METHODS: The study population comprised 18 homozygous (HoFH), 18 heterozygous (HeFH) FH patients, and 20 healthy controls. Cholesterol oxidation products (oxysterol, COPs) and main lipid classes were determined using gas chromatography-mass spectrometry. Results were expressed as percentages of total fat matter for lipid classes and percentages of total COPs for oxysterols. The principal component analysis (PCA) was also carried out, to highlight the correlation between studied parameters and groups investigated.
RESULTS: Patients (both HoFH and HeFH) showed lower content of free fatty acids (FFAs) and greater values of triacylglycerols (TAGs) in comparison to controls. HoFH showed lower monoacylglycerols (P<0.01) and higher free cholesterol (FC) (P<0.05) when compared to HeFH and controls. The total content of COPs ranged from 1.96 to 4.25 mg/dL, from 2.27 to 4.05 mg/dL, and from 0.79 to 4.12 mg/dL in healthy controls, HoFH and HeFH groups, respectively, with no significant differences between patients and controls. In general, the 7α-hydroxycholesterol (7α-HC) was greater than other COPs. However, no significant differences were found between the three studied groups. Moreover, an opposite trend was observed between 7α-HC and 7-ketocholesterol (7-KC). Additionally, when PCA was carried out, the first two PCs explained 92.13 % of the total variance, of which the PC1 describes 53.94 % of variance mainly correlated to TAGs, diacylglycerols (DAGs), and 7-KC. On the other hand, the PC2 was correlated primarily for FFAs, FC and esterified sterols (E-STE).
CONCLUSIONS: In conclusion, abnormal levels of TAGs, DAGs and 7-KC were associated with HeFH while HoFH was associated with the abnormal amount of E-STE.