Discrimination between minimally modified LDL and fully oxidized LDL using monoclonal antibodies

2021 ◽  
pp. 114103
Author(s):  
Kanokwan Lowhalidanon ◽  
Panida Khunkaewla
Keyword(s):  
Monoclonal Antibodies ◽  
Oxidized Ldl ◽  
Modified Ldl

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.

Abstract 019: Oxidized LDL and AGE-LDL in Circulating Immune Complexes Strongly Predict Progression of Carotid IMT in Type 1 Diabetes

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Kelly J Hunt ◽  
Nathaniel L Baker ◽  
Patricia Cleary ◽  
Jye-Yu Backlund ◽  
Gabriel Virella ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Immune Complexes ◽  
Internal Carotid ◽  
Oxidized Ldl ◽  
Carotid Imt ◽  
Modified Ldl ◽  
The Relationship

Many studies have demonstrated a relationship between modified LDL and cardiovascular disease. Nonetheless, few studies have examined the relationship between modified LDL immune complexes (IC) and cardiovascular disease, even though the majority of modified LDL in circulation is bound to IC. We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in individuals with type 1 diabetes. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured in a subgroup of 459 patients participating in the Diabetes Control and Complications Trial (DCCT) and it’s follow up study the Epidemiology of Diabetes Interventions and Complications (EDIC). Internal carotid intima-medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Levels of oxLDL-IC, AGE-LDL-IC and MDA-LDL-IC were moderately correlated with lipid levels [i.e., rho<0.32], but not with age. Modified LDL-IC significantly predicted having elevated internal carotid IMT (i.e., IMT ≥1.00 mm) as well as progression of IMT defined as being in the upper quintile of change from EDIC year 1 to 12 after adjusting for DCCT treatment group [intensive vs. conventional], retinopathy cohort [primary prevention vs. secondary intervention], age, gender, diabetes duration, albumin excretion rate, LDL, HDL, SBP, smoking status and IMT reader (Table). Relative to those in the lowest quartile, individuals in the upper quartile of oxLDL-IC had a 3.7-fold increased odds (CI: 1.72, 7.94) of having IMT ≥ 1.00 mm and had a 6.1-fold increased odds (CI: 2.57, 14.6) of having significant IMT progression. Parallel odds ratios for AGE-LDL-IC were 3.26 (CI: 1.57, 6.79) and 5.31 (CI: 2.23, 12.6), while results for MDA-LDL-IC were not as strong. Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intima-medial thickening in patients with type 1 diabetes.

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 Scavenger Receptors Class A-I/II and CD36 Are the Principal Receptors Responsible for the Uptake of Modified Low Density Lipoprotein Leading to Lipid Loading in Macrophages

2002 ◽  
Vol 277 (51) ◽  
pp. 49982-49988 ◽  
Author(s):  
Vidya V. Kunjathoor ◽  
Maria Febbraio ◽  
Eugene A. Podrez ◽  
Kathryn J. Moore ◽  
Lorna Andersson ◽  
...  
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Gas Chromatography Mass Spectrometry ◽  
Scavenger Receptors ◽  
Low Density ◽  
Lipid Uptake ◽  
Modified Ldl ◽  
Ldl Uptake

Modification of low density lipoprotein (LDL) can result in the avid uptake of these lipoproteins via a family of macrophage transmembrane proteins referred to as scavenger receptors (SRs). The genetic inactivation of either of two SR family members, SR-A or CD36, has been shown previously to reduce oxidized LDL uptakein vitroand atherosclerotic lesions in mice. Several other SRs are reported to bind modified LDL, but their contribution to macrophage lipid accumulation is uncertain. We generated mice lacking both SR-A and CD36 to determine their combined impact on macrophage lipid uptake and to assess the contribution of other SRs to this process. We show that SR-A and CD36 account for 75–90% of degradation of LDL modified by acetylation or oxidation. Cholesteryl ester derived from modified lipoproteins fails to accumulate in macrophages taken from the double null mice, as assessed by histochemistry and gas chromatography-mass spectrometry. These results demonstrate that SR-A and CD36 are responsible for the preponderance of modified LDL uptake in macrophages and that other scavenger receptors do not compensate for their absence.

scholarly journals Hypochlorite modified LDL are a stronger agonist for platelets than copper oxidized LDL

FEBS Letters ◽  
2000 ◽  
Vol 483 (2-3) ◽  
pp. 155-159 ◽  
Author(s):  
Ivo Volf ◽  
Astrid Roth ◽  
Julian Cooper ◽  
Thomas Moeslinger ◽  
Elisabeth Koller
Keyword(s):  
Oxidized Ldl ◽  
Modified Ldl

scholarly journals Oxidized LDL and Malondialdehyde-Modified LDL in Patients With Acute Coronary Syndromes and Stable Coronary Artery Disease

Circulation ◽  
1998 ◽  
Vol 98 (15) ◽  
pp. 1487-1494 ◽  
Author(s):  
Paul Holvoet ◽  
Johan Vanhaecke ◽  
Stefaan Janssens ◽  
Frans Van de Werf ◽  
Désiré Collen
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Acute Coronary Syndromes ◽  
Oxidized Ldl ◽  
Stable Coronary Artery Disease ◽  
Modified Ldl ◽  
Coronary Syndromes ◽  
Artery Disease

Triggering of inflammatory response by myeloperoxidase-oxidized LDLAn oral presentation of the data was given before the Congress of the Beligian Society of Internal Medicine.

2006 ◽  
Vol 84 (5) ◽  
pp. 805-812 ◽  
Author(s):  
Karim Zouaoui Boudjeltia ◽  
Ilham Legssyer ◽  
Pierre Van Antwerpen ◽  
Roger Lema Kisoka ◽  
Sajida Babar ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Oxidized Ldl ◽  
Fold Increase ◽  
Ldl Oxidation ◽  
Early Event ◽  
Modified Ldl ◽  
Tnf Α ◽  
Cell Medium ◽  
Oxidation Theory ◽  
Cellular Types

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-α by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 µg/mL and 200 µg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 µg/mL) increased the production of TNF-α 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.

scholarly journals Bisphenol a Exposure Causes Increased Oxidation of Low Density Lipoprotein (LDL) and Its Abduct in Rats

2021 ◽  
pp. 1-10
Author(s):  
Chinenye E. Oguazu ◽  
Francis C. Ezeonu ◽  
Charles C. Dike ◽  
Charles G. Ikimi
Keyword(s):  
Bisphenol A ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Diagnostic Procedures ◽  
Female Rats ◽  
Control Group ◽  
Low Density ◽  
Modified Ldl ◽  
Low Exposure

Background and Objectives: Living organisms are exposed to oxidant agents constantly from both endogenous and exogenous sources. One of such oxidant agent is Bisphenol A (BPA) and its exposure is capable to modify biomolecules and induce damages. Bisphenol A (BPA) is a contaminant with increasing exposure. It exerts toxic effects on cells.  This study investigates the possibility of BPA exposure on Low Density Lipoprotein (LDL) perturbations at prevailing low exposure doses in female albino Wistar rats, following exposure for the period of three (3) month. Materials and Methods: Total 12 groups were formed; out of which 11 experimental groups, each containing 10non-pregnant female rats were administered; 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1 mg of BPA/kgbw/day. To the 12th control group was given water.  Blood was collected from animals at the end of every week of the study and serum sample specimens analyzed by routine diagnostic procedures for oxidized LDL such as malondialdehyde modified- LDL (MDA-LDL), oxidized phospholipids LDL (OX-PL LDL), N (epsilon) (carboxymethyl) lysine-modified-LDL (CML LDL) and 4-hydroxynonenal-LDL (HNE-LDL) using Autochemical Analyzer. Results: Significantly increased concentrations of serum oxidized LDL such as MDA-LDL, OX-PL LDL, CML LDL and HNE-LDL were observed at all concentrations of BPA exposure. Conclusion:  Bisphenol A alters oxidized LDL such as MDA-LDL, OX-PL LDL, CML LDL and HNE-LDL balance and causes disturbance of internal oxidative statues.

scholarly journals Production and characterization of monoclonal antibodies to oxidized LDL

1998 ◽  
Vol 30 (1) ◽  
pp. 41-45 ◽  
Author(s):  
Kyungho Choi ◽  
Hyun Soon Lee ◽  
Hong Keun Chung
Keyword(s):  
Monoclonal Antibodies ◽  
Oxidized Ldl
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