Elimination kinetics of carbonyl-modified low density lipoproteins from bloodstream

2020 ◽  
Vol 66 (6) ◽  
pp. 437-443
Author(s):  
A.K. Tikhaze ◽  
S.P. Domogatsky ◽  
V.Z. Lankin
Keyword(s):  
Blood Plasma ◽  
Oxidized Ldl ◽  
Low Density Lipoproteins ◽  
Human Blood Plasma ◽  
Low Density ◽  
Elimination Kinetics ◽  
Pcsk9 Inhibitor ◽  
Modified Ldl ◽  
Modified Low Density Lipoproteins ◽  
Kinetics Of

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.

scholarly journals Atherogenic modification of low-density lipoproteins

2016 ◽  
Vol 62 (4) ◽  
pp. 391-402 ◽  
Author(s):  
V.N. Sukhorukov ◽  
V.P. Karagodin ◽  
A.N. Orekhov
Keyword(s):  
Blood Plasma ◽  
Human Blood ◽  
Lipid Accumulation ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Human Blood Plasma ◽  
Low Density ◽  
Modified Ldl ◽  
Intracellular Lipid Accumulation

One of the first manifestations of atherosclerosis is accumulation of extra- and intracellular cholesterol esters in the arterial intima. Formation of foam cells is considered as a trigger in the pathogenesis of atherosclerosis. Low density lipoprotein (LDL) circulating in human blood is the source of lipids accumulated in the arterial walls. This review considered features and role in atherogenesis different modified forms of LDL: oxidized, small dense, electronegative and especially desialylated LDL. Desialylated LDL of human blood plasma is capable to induce lipid accumulation in cultured cells and it is atherogenic. LDL possesses numerous alterations of protein, carbohydrate and lipid moieties and therefore can be termed multiple-modified LDL. Multiple modification of LDL occurs in human blood plasma and represents a cascade of successive changes in the lipoprotein particle: desialylation, loss of lipids, reduction in the particle size, increase of surface electronegative charge, etc. In addition to intracellular lipid accumulation, stimulatory effects of naturally occurring multiple-modified LDL on other processes involved in the development of atherosclerotic lesions, namely cell proliferation and fibrosis, were shown.

scholarly journals Development of Capture Assays for Different Modifications of Human Low-Density Lipoprotein

2005 ◽  
Vol 12 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Gabriel Virella ◽  
M. Brooks Derrick ◽  
Virginia Pate ◽  
Charlyne Chassereau ◽  
Suzanne R. Thorpe ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Gas Chromatography Mass Spectrometry ◽  
Low Density ◽  
Modified Ldl ◽  
Capture Assay ◽  
Carboxymethyl Lysine

ABSTRACT Antibodies to malondialdehyde (MDA)-modified low-density lipoprotein (LDL), copper-oxidized LDL (oxLDL), N ε(carboxymethyl) lysine (CML)-modified LDL, and advanced glycosylation end product (AGE)-modified LDL were obtained by immunization of rabbits with in vitro-modified human LDL preparations. After absorption of apolipoprotein B (ApoB) antibodies, we obtained antibodies specific for each modified lipoprotein with unique patterns of reactivity. MDA-LDL antibodies reacted strongly with MDA-LDL and also with oxLDL. CML-LDL antibodies reacted strongly with CML-LDL and also AGE-LDL. oxLDL antibodies reacted with oxLDL but not with MDA-LDL, and AGE-LDL antibodies reacted with AGE-LDL but not with CML-LDL. Capture assays were set with each antiserum, and we tested their ability to capture ApoB-containing lipoproteins isolated from precipitated immune complexes (IC) and from the supernatants remaining after IC precipitation (free lipoproteins). All antibodies captured lipoproteins contained in IC more effectively than free lipoproteins. Analysis of lipoproteins in IC by gas chromatography-mass spectrometry showed that they contained MDA-LDL and CML-LDL in significantly higher concentrations than free lipoproteins. A significant correlation (r = 0.706, P < 0.019) was obtained between the MDA concentrations determined by chemical analysis and by the capture assay of lipoproteins present in IC. In conclusion, we have developed capture assays for different LDL modifications in human ApoB/E lipoprotein-rich fractions isolated from precipitated IC. This approach obviates the interference of IC in previously reported modified LDL assays and allows determination of the degree of modification of LDL with greater accuracy.

Expression of receptors for native and chemically modified low-density lipoproteins in brain microvessels

FEBS Letters ◽  
1997 ◽  
Vol 401 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Marco Lucarelli ◽  
Massimo Gennarelli ◽  
Patrizia Cardelli ◽  
Giuseppe Novelli ◽  
Sigfrido Scarpa ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Chemically Modified ◽  
Brain Microvessels ◽  
Modified Low Density Lipoproteins

Effects of Modified Low-Density Lipoproteins on Human Retinal Pericyte Survival

2005 ◽  
Vol 1043 (1) ◽  
pp. 390-395 ◽  
Author(s):  
WEIWEI SONG ◽  
JEREMY L. BARTH ◽  
KANGMO LU ◽  
YONGXIN YU ◽  
YAN HUANG ◽  
...  
Keyword(s):  
Low Density Lipoproteins ◽  
Low Density ◽  
Modified Low Density Lipoproteins

Oxidized low-density lipoproteins and microvascular responses to ischemia-reperfusion

1996 ◽  
Vol 271 (6) ◽  
pp. H2508-H2514 ◽  
Author(s):  
L. Liao ◽  
N. R. Harris ◽  
D. N. Granger
Keyword(s):  
Mast Cell ◽  
Oxidized Ldl ◽  
Ischemia Reperfusion ◽  
Low Density Lipoproteins ◽  
Mast Cell Degranulation ◽  
Low Density ◽  
Oxidized Low Density Lipoproteins ◽  
Rat Mesentery ◽  
Albumin Leakage ◽  
Wistar Kyoto

The objective of this study was to determine whether ischemia and reperfusion (I/R) and/or chronic arterial hypertension potentiates the leukocyte-endothelial cell adhesion (LECA) and microvascular dysfunction elicited by oxidized low-density lipoproteins (ox-LDL). Mast cell degranulation, leukocyte adherence and emigration, and albumin leakage were monitored in postcapillary venules of rat mesentery. Intra-arterial infusion of copper-oxidized LDL (Cu-LDL), at a concentration that does not directly affect the microvasculature, significantly enhanced the I/R-induced recruitment of adherent and emigrated leukocytes but does not affect the increased albumin leakage and mast cell degranulation responses normally observed after I/R. Infusion of a higher concentration of Cu-LDL in nonischemic mesentery of either normotensive Wistar-Kyoto or spontaneously hypertensive rats elicited significant yet similar increases in LECA, mast cell degranulation, and albumin leakage. These findings indicate that 1) ox-LDL act synergistically with I/R to promote leukocyte recruitment in postcapillary venules but without an accompanying exacerbation of albumin leakage, and 2) ox-LDL do not elicit a more intense inflammatory response in the microvasculature of hypertensive versus normotensive animals.

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