modified ldl
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Author(s):  
Chinenye E. Oguazu ◽  
Francis C. Ezeonu ◽  
Charles C. Dike ◽  
Charles G. Ikimi

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.


2021 ◽  
Vol 18 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  

Aims: To investigate the role of glyoxal modified LDL in the immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardi-ovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the im-munogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high-performance liquid chromatography and electron microscopy. Immuniza-tion studies were carried in New Zealand rabbits. The presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects was analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha-helix content of LDL; increased β sheet formation; increased carbon-yl content and decreased free lysine and arginine content. Modified LDL showed aggrega-tion, generation of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggre-gates. It exhibited high antigenicity and generated specific immune responses that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti-glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited the highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the genera-tion of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.


Author(s):  
Su Duy Nguyen ◽  
Emilia A. Korhonen ◽  
Martina B. Lorey ◽  
Laura Hakanpää ◽  
Mikko I. Mäyränpää ◽  
...  

Author(s):  
Huaicheng Chen ◽  
Tao Yan ◽  
Zongming Song ◽  
Shilong Ying ◽  
Beibei Wu ◽  
...  

AbstractModified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.


2021 ◽  
Vol 22 ◽  
Author(s):  
Md Masum Rizwee ◽  
Minhal Abidi ◽  
Safia Habib ◽  
Abdul Rouf Mir ◽  
Asif Ali ◽  
...  

Aims: To investigate role of glyoxal modified LDL in immunopathology of diabetes and cardiovascular disease. Background: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. Objective: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). Methods: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. Presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects were analyzed by ELISA. Results: Glyoxal altered the structural integrity of LDL and lead to the formation of AGEs. It decreased the alpha helix content of LDL; increased β sheet formation; increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε-(Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti- glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited highest binding with glyoxal modified LDL. Conclusion: Glyoxal modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.


2020 ◽  
Vol 315 ◽  
pp. e148
Author(s):  
V.R. Sant'Anna ◽  
R. Souza ◽  
A. Barbosa ◽  
J.M. Sousa ◽  
A.C. Camargo ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V.N Sukhorukov ◽  
Y.V Markina ◽  
A.M Markin ◽  
M Bagheri Ekta ◽  
V.A Khotina ◽  
...  

Abstract Background Foam cell formation caused by modified LDL is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. 10 inflammation-related master regulators, which were involved in the cholesterol accumulation in cultured macrophages induced by the incubation with modified LDL, have been identified. Objective We hypothesised that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. Methods Cholesterol accumulation was evaluated in primary macrophages with master regulator genes knock-downed by siRNA for either IL15, EIF2AK3, F2RL1, TSPYL2, or ANXA1. Analysis of enriched transcription factor binding sites in promoters of differentially expressed genes and identification of master regulators in the signal transduction network were performed with TRANSFAC and TRANSPATH databases. Results Genes which were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads were determined. Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages, whereas atherogenic naturally occurring LDL caused significant cholesterol accumulation in the control cells. The ANXA1 gene knock-down caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. Conclusions The results, showing that inflammatory response and the cholesterol accumulation are related, may confirm our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Russian Science Foundation


2020 ◽  
pp. 155-162
Author(s):  
L. Cominacini ◽  
U. Garbin ◽  
A. Fratta Pasini ◽  
A. Davoli ◽  
M. Campagnola ◽  
...  
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