Abstract 451: HPODE Upregulates the Expression of Secretory Phospholipase A2 Group IIA in Rat Smooth Muscle Cells. Potential Contribution to the Progression of Atherosclerosis

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Zhaohui Yang ◽  
Chandrakala Aluganti Narasimhulu ◽  
Xueting Jiang ◽  
Sampath Parthasarathy
Keyword(s):  
Phospholipase A2 ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Foam Cell Formation ◽  
Potential Contribution ◽  
Dependent Manner ◽  
Secretory Phospholipase A2 ◽  
Concentration Dependent Manner ◽  
Decomposition Products ◽  
Secretory Phospholipase

Introduction Peroxidized lipids have been suggested to contribute to atherosclerosis in a number of ways. Accumulating evidence indicates that Group IIA secretory phospholipase A2 (sPLA2-IIA) may contribute to the atherogenic process and serve as markers for cardiovascular diseases. However, the relationship between lipid peroxides and sPLA2-IIA remain poorly identified. Hypothesis Peroxidized lipids such as HPODEs might induce the expression of sPLA2-IIA and enhance the uptake of LDL, thereby contributing to lipid accumulation. Methods Different concentrations of HPODE (0 μM, 12.5μM, 25μM) or oxidized -LDL (ox-LDL) (25μg/ml) were incubated with SMCs at 37°C. Real-time PCR was used to assay gene expression. The degradation of HPODE and ox-LDL was also monitored by the loss of peroxides and conjugated dienes. The formation of HPODE decomposition products was followed by electrospray mass spectrometry. Results Incubation of SMCs with HPODE resulted in an up-regulation of sPLA2-IIA mRNA expression in a concentration dependent manner. However, ox-LDL had limited or no effects in the expression of sPLA2. In addition, SMCs and peritoneal mouse macrophages pretreated with HPODE for 8hrs followed by DiI-LDL (20μg/ml) showed an increase in accumulation of labeled LDL as compared to control. We also noted that HPODE was decomposed by SMCs in hours as compared to no cell incubations. However, incubation of peroxidized lipids in the form of ox-LDL resulted in poor decomposition of the peroxides. Conclusion SMCs may break down the peroxidized fatty acids leading to the formation of simple compounds such as aldehydes and carboxylic acids. HPODE or its decomposition products may induce the expression of sPLA2-II and enhance foam cell formation.

scholarly journals Atheroprotective action of a modified organoselenium compound: in vitro evidence

2016 ◽  
Vol 88 (3 suppl) ◽  
pp. 1953-1965 ◽  
Author(s):  
JADE DE OLIVEIRA ◽  
MARCOS R. STRALIOTTO ◽  
GIANNI MANCINI ◽  
CLAUDIA P. FIGUEIREDO ◽  
ANTÔNIO L. BRAGA ◽  
...  
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Organoselenium Compound ◽  
Organoselenium Compounds ◽  
Concentration Dependent Manner

ABSTRACT Oxidation of low-density lipoprotein (LDL) has been strongly suggested to play a significant role in the pathogenesis of atherosclerosis. Thus, reducing LDL oxidation is a potential approach to decrease the risk of the atherosclerosis. Organoselenium compounds have demonstrated promising atheroprotective properties in experimental models. Herein, we tested the in vitro atheroprotective capability of a modified organoselenium compound, Compound HBD, in protecting isolated LDL from oxidation as well as foam cells formation. Moreover, the glutathione peroxidase (GPx)-like activity of Compound HBD was analyzed in order to explore the mechanisms related to the above-mentioned protective effects. The Compound HBD in a concentration-dependent manner reduced the Cu2+-induced formation of conjugated dienes. The protein portion from LDL were also protected from Cu2+-induced oxidation. Furthermore, the Compound HBD efficiently decreased the foam cell formation in J774 macrophage cells exposed to oxidized LDL. We found that the atheroprotective effects of this compound can be, at least in part, related to its GPx-like activity. Our findings demonstrated an impressive effect of Compound HBD against LDL-induced toxicity, a further in vivo study to investigate in more detail the antioxidant and antiatherogenic effects of this compound could be considered.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

scholarly journals Role of pyruvate kinase M2 in oxidized LDL-induced macrophage foam cell formation and inflammation

2020 ◽  
Vol 61 (3) ◽  
pp. 351-364 ◽  
Author(s):  
Amit Kumar ◽  
Priya Gupta ◽  
Minakshi Rana ◽  
Tulika Chandra ◽  
Madhu Dikshit ◽  
...  
Keyword(s):  
Protein Expression ◽  
Pyruvate Kinase ◽  
Foam Cell ◽  
Aerobic Glycolysis ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Macrophage Foam Cell ◽  
Pyruvate Kinase M2

Pyruvate kinase M2 (PKM2) links metabolic and inflammatory dysfunction in atherosclerotic coronary artery disease; however, its role in oxidized LDL (Ox-LDL)-induced macrophage foam cell formation and inflammation is unknown and therefore was studied. In recombinant mouse granulocyte-macrophage colony-stimulating factor-differentiated murine bone marrow-derived macrophages, early (1–6 h) Ox-LDL treatment induced PKM2 tyrosine 105 phosphorylation and promotes its nuclear localization. PKM2 regulates aerobic glycolysis and inflammation because PKM2 shRNA or Shikonin abrogated Ox-LDL-induced hypoxia-inducible factor-1α target genes lactate dehydrogenase, glucose transporter member 1, interleukin 1β (IL-1β) mRNA expression, lactate, and secretory IL-1β production. PKM2 inhibition significantly increased Ox-LDL-induced ABCA1 and ABCG1 protein expression and NBD-cholesterol efflux to apoA1 and HDL. PKM2 shRNA significantly inhibited Ox-LDL-induced CD36, FASN protein expression, DiI-Ox-LDL binding and uptake, and cellular total cholesterol, free cholesterol, and cholesteryl ester content. Therefore, PKM2 regulates lipid uptake and efflux. DASA-58, a PKM2 activator, downregulated LXR-α, ABCA1, and ABCG1, and augmented FASN and CD36 protein expression. Peritoneal macrophages showed similar results. Ox-LDL induced PKM2- SREBP-1 interaction and FASN expression in a PKM2-dependent manner. Therefore, this study suggests a role for PKM2 in Ox-LDL-induced aerobic glycolysis, inflammation, and macrophage foam cell formation.

Rubus coreanusInhibits Oxidized-LDL Uptake by Macrophages Through Regulation of JNK Activation

2012 ◽  
Vol 40 (05) ◽  
pp. 967-978 ◽  
Author(s):  
Bidur Bhandary ◽  
Geum-Hwa Lee ◽  
Byung-Ok So ◽  
Sun-Young Kim ◽  
Min-Gul Kim ◽  
...  
Keyword(s):  
Foam Cell ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Blood Stasis ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Rubus Coreanus ◽  
Dose Dependent

Oxidized low-density lipoprotein (oxLDL) contributes to atherosclerosis in part by being taken up into macrophages via scavenger receptors and leading to foam cell formation. Herbal compounds that have been used to treat blood stasis (a counterpart of atherosclerosis) for centuries include extracts of medicinal plants in the Rosaceae and Leguminosae families. In this study, we investigated the effect of the unripe Rubus coreanus (Korean black raspberry) fruit extract on oxLDL uptake by murine macrophage cells. In the presence of Rubus coreanus extract (RCE), Dil-labeled oxLDL uptake was inhibited in a dose-dependent manner. SP600125, a specific JNK inhibitor, inhibited the uptake of Dil-oxLDL into macrophages. RCE also inhibited JNK phosphorylation in a time- and dose-dependent manner in macrophages treated with oxLDL. These results indicate that among the mitogen-activated protein kinases, JNK phosphorylation is inhibited by RCE, which is likely the mechanism underlying the RCE-induced inhibition of oxLDL uptake by macrophages.

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