Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland.
Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Lodz, Poland.
Sci Rep. 2024 Jan 31;14(1):2564. doi: 10.1038/s41598-024-52571-w.
Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal-dominant inherited disorder associated with atherosclerotic cardiovascular disease (ASCVD). HeFH subjects have a higher lipoprotein(a), i.e. Lp(a), concentration than the general population. Patients with FH are exposed to elevated levels of LDL from birth and ox-LDL may induce other oxidation pathways. The aim of the study was to determine the levels of markers of oxidative stress and DNA damage in patients with HeFH and describe the effect of Lp(a) on the resulting damage. Higher DNA damage was identified in patients with HeFH compared to the normolipidemic ones, and ASCVD was associated with greater damage. Oxidative stress markers were elevated in HeFH patients; however, only ox-LDL was higher in the ASCVD group and its level correlated with DNA damage. A positive correlation was found between DNA damage and Lp(a) concentration in the HeFH patients. Higher levels of Lp(a) were associated with greater DNA damage, especially in patients with HeFH and ASCVD. In HeFH patients, the optimal Lp(a) cut-off point associated with ASCVD is > 23.45 nmol/L, i.e. much lower than for the general population; however this cut-off point needs validation in a larger group of HeFH patients.
杂合子家族性高胆固醇血症(HeFH)是一种常见的常染色体显性遗传性疾病,与动脉粥样硬化性心血管疾病(ASCVD)有关。HeFH 患者的脂蛋白(a),即 Lp(a)浓度高于一般人群。FH 患者从出生起就暴露在高水平的 LDL 中,氧化 LDL 可能会诱导其他氧化途径。本研究旨在确定 HeFH 患者氧化应激和 DNA 损伤标志物的水平,并描述 Lp(a)对由此产生的损伤的影响。与血脂正常的患者相比,HeFH 患者的 DNA 损伤更高,而 ASCVD 与更大的损伤有关。HeFH 患者的氧化应激标志物升高;然而,只有 ASCVD 组的 ox-LDL 更高,其水平与 DNA 损伤相关。HeFH 患者的 DNA 损伤与 Lp(a)浓度呈正相关。Lp(a)水平较高与 DNA 损伤较大有关,尤其是在 HeFH 和 ASCVD 患者中。在 HeFH 患者中,与 ASCVD 相关的最佳 Lp(a)截断值>23.45 nmol/L,远低于一般人群;然而,这一截断值需要在更大的 HeFH 患者群体中进行验证。