Lipid oxidation in atherogenesis: an overview

2004 ◽  
Vol 32 (1) ◽  
pp. 134-138 ◽  
Author(s):  
W. Jessup ◽  
L. Kritharides ◽  
R. Stocker
Keyword(s):  
Vitamin E ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Oxidation Products ◽  
Oxidation Reactions ◽  
Track Record ◽  
Oxidized Lipoproteins ◽  
Oxidation Theory

The ‘oxidation theory’ for atherosclerosis proposes that lipid and/or protein oxidation products are responsible for lesion formation/development. The major target for oxidation is suggested to be intimal low-density lipoprotein. This idea was stimulated by the pro-atherogenic properties of in vitro oxidized lipoproteins, such as stimulation of chemotaxis and sterol accumulation in macrophages, adhesion molecule expression on endothelial cells and apoptosis of several cell types. It was supported by detection of oxidation products in lesion lipoproteins, although these are (in general) less heavily oxidized and their biological activity is less rigorously defined than for their in vitro oxidized counterparts. Lesion lipids contain products generated by both enzymic and non-enzymic oxidation reactions; the majority are generated non-enzymically. The type and source of oxidant involved has been the subject of much speculation and is not resolved. The oxidation theory predicts that appropriate antioxidants will protect against atherosclerosis. Vitamin E has been used in several animal and human studies, but to date has shown little evidence of anti-atherosclerotic potential. However, lack of knowledge of the oxidant(s) driving lesion oxidation and the complexity of the anti- and pro-oxidant properties of vitamin E may explain its disappointing track record to date. These subjects require more rigorous study before the oxidation theory can be fairly tested.

scholarly journals Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant

1992 ◽  
Vol 288 (2) ◽  
pp. 341-344 ◽  
Author(s):  
V W Bowry ◽  
K U Ingold ◽  
R Stocker
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin E ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peroxyl Radicals ◽  
Careful Examination ◽  
Early Event ◽  
Low Density ◽  
Tocopheroxyl Radical

Uptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atherosclerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease. However, a careful examination of lipid peroxidation in LDL induced by a steady flux of aqueous peroxyl radicals has demonstrated that, following consumption of endogenous ubiquinol-10, the rate of peroxidation (i) declines as vitamin E is consumed, (ii) is faster in the presence of vitamin E than following its complete consumption, (iii) is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or by diet, and (iv) is virtually independent of the applied radical flux. We propose that perodixation is propagated within lipoprotein particles by reaction of the vitamin E radical (i.e. alpha-tocopheroxyl radical) with polyunsaturated fatty acid moieties in the lipid. This lipid peroxidation mechanism, which can readily be rationalized by the known chemistry of the alpha-tocopheroxyl radical and by the radical-isolating properties of fine emulsions such as LDL, explains how reagents which reduce the alpha-tocopheroxyl radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL.

scholarly journals Novel Plaque Enriched Long Noncoding RNA in Atherosclerotic Macrophage Regulation (PELATON)

2020 ◽  
Vol 40 (3) ◽  
pp. 697-713 ◽  
Author(s):  
John Hung ◽  
Jessica P. Scanlon ◽  
Amira D. Mahmoud ◽  
Julie Rodor ◽  
Margaret Ballantyne ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Noncoding Rna ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Lipid Uptake ◽  
Unstable Plaque ◽  
Inflammatory Bowel ◽  
Unstable Atherosclerotic Plaque

Objective: Long noncoding RNAs (lncRNAs) are an emergent class of molecules with diverse functional roles, widely expressed in human physiology and disease. Although some lncRNAs have been identified in cardiovascular disease, their potential as novel targets in the prevention of atherosclerosis is unknown. We set out to discover important lncRNAs in unstable plaque and gain insight into their functional relevance. Approach and Results: Analysis of RNA sequencing previously performed on stable and unstable atherosclerotic plaque identified a panel of 47 differentially regulated lncRNAs. We focused on LINC01272, a lncRNA upregulated in unstable plaque previously detected in inflammatory bowel disease, which we termed PELATON (plaque enriched lncRNA in atherosclerotic and inflammatory bowel macrophage regulation). Here, we demonstrate that PELATON is highly monocyte- and macrophage-specific across vascular cell types, and almost entirely nuclear by cellular fractionation (90%–98%). In situ hybridization confirmed enrichment of PELATON in areas of plaque inflammation, colocalizing with macrophages around the shoulders and necrotic core of human plaque sections. Consistent with its nuclear localization, and despite containing a predicted open reading frame, PELATON did not demonstrate any protein-coding potential in vitro. Functionally, knockdown of PELATON significantly reduced phagocytosis, lipid uptake and reactive oxygen species production in high-content analysis, with a significant reduction in phagocytosis independently validated. Furthermore, CD36, a key mediator of phagocytic oxLDL (oxidized low-density lipoprotein) uptake was significantly reduced with PELATON knockdown. Conclusions: PELATON is a nuclear expressed, monocyte- and macrophage-specific lncRNA, upregulated in unstable atherosclerotic plaque. Knockdown of PELATON affects cellular functions associated with plaque progression.

Stem cell intervention ameliorates epigallocatechin-3-gallate/lipopolysaccharide-induced hepatotoxicity in mice

2015 ◽  
Vol 34 (11) ◽  
pp. 1180-1194
Author(s):  
IG Saleh ◽  
Z Ali ◽  
MA Hammad ◽  
FD Wilson ◽  
FM Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transforming Growth Factor ◽  
Retinoic Acid Receptor ◽  
Low Density Lipoprotein ◽  
Embryonic Stem ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Transforming Growth Factor Β1 ◽  
Oxidative Stress Biomarkers

Stem cells are identified as a novel cell therapy for regenerative medicine because of their ability to differentiate into many functional cell types. We have shown earlier a new model of hepatotoxicity in mice by administering (1500 mg/kg) epigallocatechin-3-gallate (EGCG) intragastric (IG) for 5 days after a single intraperitoneal dose (6 mg/kg) of lipopolysaccharide (LPS). In this study, we aimed to study the effect of intrahepatic (IH) injection of mouse embryonic stem cells (MESCs) on the hepatotoxicity induced by EGCG/LPS in mice. Mice were administered EGCG/LPS and rested for 3 days. MESCs were obtained from American Type Culture Collection and cultured in vitro for 4 days. Stem cells were injected IH. Seven days later, a single dose of LPS (6 mg/kg) followed by daily doses of IG administration of EGCG were re-administered for 5 days. At the end of the experiment, blood samples were collected for analysis of biochemical parameters associated with liver. Results showed that the group of mice that were administered MESCs prior to EGCG/LPS showed lower levels of alanine amino transferase, alkaline phosphatase, and bilirubin, higher albumin/globulin ratio, and less remarkable histopathological lesions. Also, that group of mice showed less expression of oxidative stress biomarkers (oxidized low-density lipoprotein Ox.LDL and chemokine CXCL16), less expression of nuclear protein receptors (retinoic acid receptor and retinoid X receptor), and less expression of inflammatory biomarkers (tumor necrosis factor α and transforming growth factor β1) compared with other groups of mice that were not given MESCs. In conclusion, MESCs can ameliorate EGCG/LPS-induced hepatotoxicity in mice.

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