Elimination kinetics of carbonyl-modified low density lipoproteins from bloodstream

Abstract

The elimination kinetics of carbonyl-modified low density lipoproteins (LDL) from rabbit bloodstream was studied using isolated LDL of rabbits and humans after preliminary biotinylation or labeling with FITZ. LDL from rabbit or human blood plasma were isolated using differential ultracentrifugation in a density gradient, and then LDL were labeled using biotinylation or FITZ, after which they were modified with various low molecular weight natural dicarbonyls: malondialdehyde (MDA), glyoxal or methylglyoxal. Native and dicarbonyl-modified biotinylated or FITZ-labeled LDL were injected into the ear vein of rabbits and blood samples were taken at certain intervals. To determine the content of biotinylated LDL in blood plasma, an enzyme immunoassay was performed; FITZ-labeled LDL were determined by spectra fluorescence. It is shown that glyoxal- and methylglyoxal-modified LDL in rabbits and humans circulated in the bloodstream for almost the same time as native (unmodified) LDL. At the same time, MDA-modified rabbit and human LDL were extremely quickly eliminated from the rabbit bloodstream. Dicarbonyl-modified LDL from the donors blood plasma were not associated with the red blood cells and endothelial cells. It has been shown that using the kits Oxidized LDL ELISA (“Mercodia”, Sweden), it is possible to identify mainly MDA-modified LDL. The level of MDA-modified LDL in the blood plasma of CHD patients sharply decreases during therapy with the hypocholesterolemic drug the PCSK9 inhibitor (evulokumab), which activates LDL reutilization in the liver cells. These results explain the extreme drop in the level of MDA-modified LDL by their increased utilization in hepatocytes. The results obtained indicate a high atherogenicity of glyoxal- and methylglyoxal-modified LDL, long-term circulating in the bloodstream.

Impact of summer heat waves on key parameters of oxidative stress in patients with coronary artery disease

“…1, 2) практически идентичен. Увеличение уровня МДА в плазме крови рассматривается как характерный признак развития окислительного стресса [9][10][11], причем снижение активности гидропероксид-восстанавли-вающих ферментов в эритроцитах (CAT и GSH-Px) может быть следствием модификации молекул этих ферментов накапливающимися низкомолекулярными карбонильными соединениями, такими как МДА [22,26] и его метаболические предшественники -гидроксиноненали [9][10][11]. В связи с этим, казалось бы, парадоксальное увеличение активности эритроцитарной Cu,Zn-SOD при экспериментальной гипертермии [16,17] который является мощным ингибитором антиоксидантных ферментов CAT и GSH-Px [9][10][11].…”

“…рис. 2) может быть объяснено их экстремально высоким клиренсом у млекопитающих [26] вследствие активной утилизации скевенжер-рецепторами купферовских клеток печени [27].…”