Department for Free Radical Biochemistry, E.I. Chazov' National Medical Research Center of Cardiology, Russian Ministry of Health, Moscow 121552, Russia.
Research Institute of Medical Primatology, National Research Center "Kurchatov' Institute", Sochi 354376, Russia.
Int J Mol Sci. 2023 Jun 21;24(13):10471. doi: 10.3390/ijms241310471.
The kinetics of elimination of various dicarbonyl-modified low-density lipoproteins from the bloodstream of monkeys were investigated. The low-density lipoproteins (LDL) in the monkey blood plasma were isolated by density gradient ultracentrifugation and labeled in vitro with the fluorescent dye FITC; thereupon, they were modified with different natural low molecular-weight dicarbonyls: malondialdehyde (MDA), glyoxal, or methylglyoxal. The control native FITC-labeled LDL and dicarbonyl-modified FITC-labeled LDL were injected into the monkey's ulnar vein; thereafter, blood samples were taken at fixed time intervals during 24 h. The plasma level of FITC-labeled LDL was determined with spectrofluorimetry. The study established that glyoxal- and monkeysglyoxal-labeled LDL circulated in monkey virtually at the same time as native (non-modified) LDL. In contrast, MDA-modified LDL disappeared from the blood extremely rapidly. Administration of the PCSK9 inhibitor involocumab (which increases LDL utilization) to patients with coronary heart disease (CHD) was found to significantly reduce levels of MDA-modified LDL.
研究了各种二羰基修饰的低密度脂蛋白（LDL）从猴子血液中消除的动力学。通过密度梯度超速离心从猴子血浆中分离 LDL，并在体外用荧光染料 FITC 标记；随后，用不同的天然低分子量二羰基化合物：丙二醛（MDA）、乙二醛或甲基乙二醛对其进行修饰。将对照的天然 FITC 标记 LDL 和二羰基修饰的 FITC 标记 LDL 注入猴子的尺骨静脉；此后，在 24 小时内的固定时间间隔采集血液样本。用荧光分光光度法测定血浆中 FITC 标记 LDL 的水平。研究表明，乙二醛和甲基乙二醛修饰的 LDL 在猴子体内的循环时间与天然（未修饰）LDL 几乎相同。相比之下，MDA 修饰的 LDL 从血液中迅速消失。在冠心病（CHD）患者中给予 PCSK9 抑制剂依洛尤单抗（可增加 LDL 的利用）可显著降低 MDA 修饰的 LDL 水平。
