Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Germany; LIFE-Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany.
Research Laboratories and Clinic of Visceral, Transplantation, Thoracic, and Vascular Surgery, Leipzig University and University Hospital Leipzig, Germany.
Atherosclerosis. 2020 Feb;295:18-24. doi: 10.1016/j.atherosclerosis.2019.12.018. Epub 2019 Dec 20.
Circulating sterols result either from cholesterol (CH) synthesis or intestinal uptake. They are mainly esterified and can be oxygenated. Sterols accumulate in atherosclerotic plaques whereby their clinical impact is uncertain. Here, we determined associations between circulating and plaque sterol levels in patients with advanced carotid artery stenosis in respect to a prior ischemic event and statin treatment.
Free and esterified CH, CH precursors and plant sterols as well as oxysterols were quantified by liquid chromatography-tandem mass spectrometry in 63 consecutive patients undergoing carotid endarterectomy.
CH, CH precursors, plant sterols and oxysterols accumulated in carotid artery plaques. Absolute circulating sterol levels were not predictive for their corresponding plaque levels. After normalisation to CH, plant sterol but not oxysterol levels correlated between plasma and plaques. Among the circulating sterols, oxysterols occurred proportionally less in plaques. Furthermore, CH and plant sterols were less esterified in plaques than in plasma. Patients who experienced a prior ischemic event (n = 29) and asymptomatic patients had, except for lanosterol, comparable circulating sterol levels. In contrast, the absolute plaque levels of free CH, CH precursors and plant sterols as well as oxysterols were increased in symptomatic compared to asymptomatic patients. These differences remained significant for free CH, precursors and 3 out of 4 analyzed plant sterols after adjustment to the most influencing covariates - statin treatment, type 2 diabetes and age.
Increased absolute plaque levels of free CH, precursors and plant sterols predict an ischemic event in patients with advanced carotid artery stenosis.
循环甾醇源自胆固醇（CH）合成或肠道摄取。它们主要酯化，并可被氧化。甾醇在动脉粥样硬化斑块中积累，其临床影响尚不确定。在此，我们在 63 例接受颈动脉内膜切除术的颈动脉严重狭窄患者中，根据既往缺血事件和他汀类药物治疗，确定了循环和斑块甾醇水平之间的相关性。
采用液相色谱-串联质谱法定量检测 63 例连续患者的游离和酯化 CH、CH 前体和植物甾醇以及氧化甾醇。
CH、CH 前体、植物甾醇和氧化甾醇在颈动脉斑块中积累。绝对循环甾醇水平与相应的斑块水平没有预测关系。经 CH 归一化后，植物甾醇而非氧化甾醇在血浆和斑块之间存在相关性。在循环甾醇中，氧化甾醇在斑块中的比例较小。此外，与血浆相比，CH 和植物甾醇在斑块中酯化程度较低。经历过既往缺血事件（n=29）和无症状患者的除了羊毛甾醇外，具有相似的循环甾醇水平。相比之下，与无症状患者相比，有症状患者的游离 CH、CH 前体和植物甾醇以及氧化甾醇的绝对斑块水平增加。在调整最具影响的协变量（他汀类药物治疗、2 型糖尿病和年龄）后，这些差异仍然在游离 CH、前体和 4 种分析的植物甾醇中的 3 种中具有统计学意义。
在颈动脉严重狭窄的患者中，游离 CH、前体和植物甾醇的绝对斑块水平增加预示着缺血事件的发生。
