Oxidized lipoproteins and macrophages

Jessup, Wendy; Wilson, Paul; Gaus, Katharina; Kritharides, L.

doi:10.1016/s1537-1891(02)00174-x

Cited by 40 publications

(30 citation statements)

References 82 publications

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“…Conversely, other studies have showed that 7-KC inhibits the export of cholesterol to HDL, accumulating cholesterol in cells (Jessup et al, 2002).…”

Section: D) Sterol Transport: Stimulation and Inhibitionmentioning

confidence: 87%

Oxysterols: A world to explore

Otaegui-Arrazola

Menéndez-Carreño

Ansorena

et al. 2010

Food and Chemical Toxicology

202

185

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Oxysterols (oxidized derivatives of cholesterol an phytosterols) can be generated in the human organism through different oxidation processes, some requiring enzymes.Furthermore, oxysterols are also present in food due to lipid oxidation reactions caused by heating treatments, contact with oxygen, exposure to sunlight, etc., and they could be absorbed from the diet, at different rates depending on their side chain lenght.In the organism, oxysterols can follow different routes: secreted into the intestinal lumen, esterified and distributed by lipoproteins to different tissues or degraded, maily in the liver. Cholesterol oxidation products (COPs) have shown citotoxicity, apoptotic and pro-inflammatory effects and they have also been linked with chronic diseases including atherosclerotic and neurodegenerative processess. In the case of phytosterols oxidation products (POPs), the evidences for toxic effects need more research. Nevertheless, current knowledge suggest their relation to cytotoxic and proapoptotic effects, although at higher concentrations than COPs.Recently, new beneficial biological activities of oxysterols are being under research. Whereas COPs are associated with cholesterol homeostasis mediated by different mechanisms, the implication of POPs is not clear yet.Available literature on sources of oxysterols in the organism, metabolism, toxicity and potential benefitial effects of these compounds are reviewed in this paper.2

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“…Conversely, other studies have showed that 7-KC inhibits the export of cholesterol to HDL, accumulating cholesterol in cells (Jessup et al, 2002).…”

Section: D) Sterol Transport: Stimulation and Inhibitionmentioning

confidence: 87%

Oxysterols: A world to explore

Otaegui-Arrazola

Menéndez-Carreño

Ansorena

et al. 2010

Food and Chemical Toxicology

202

185

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“…In cultured RPE cells, as in other cell types, 7KCh is able to induce the formation and release of The infl ammatory role of 7KCh has been studied in a variety of cell types, such as monocytes/macrophages ( 92,93 ), astrocytes ( 94 ), vascular endothelial cells ( 95,96 ), vascular smooth muscle cells (VSMCs) ( 97,98 ), fi broblasts ( 99 ), and retinal cells ( 8, 9, 100, 101 ) from different mammals. In culture, 7KCh is able to induce the transcription and release of proinfl ammatory cytokines such as VEGF ( 9, 97 , 102 ), interleukin (IL)-1 ( 95 ), IL-6 ( 103 ), and IL-8 ( 8, 9, 104-106 ) in different cell types.…”

Section: Pharmacological Properties Of 7kchmentioning

confidence: 99%

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

Rodríguez

Larráyoz

2010

Journal of Lipid Research

121

115

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Journal of Lipid Research Volume 51, 20102847 their actions affect the retina and the retinal pigment epithelium (RPE) ( 8-10 ). One particular oxysterol, 7-ketocholesterol (7KCh), has been found more abundantly than other oxysterols in the retina ( 9, 10 ). This oxysterol is known to have potent pharmacological properties that lead to infl ammation and cell death in a variety of cell types ( 1-10 ). This review will focus on what is known about this molecule and the potential implications of its presence in the retina. The retina is a light-capturing tissue that contains at least 5 cell classes and more than 50 different cell types, each performing unique functions that ultimately provide the visual centers in the brain the information to achieve image formation and visual perception. The retina faces a unique photooxidative environment that generates challenges not encountered by other neurological tissues or organs. Phototransduction requires the retina to have a high metabolic rate ( 11 ) and multiple and complex membrane structures ( 12 ). The photoreceptor outer segments are enriched in the highly photosensitive docosahexaenoic acid and other Abstract This review will discuss the formation and potential implications of 7-ketocholesterol (7KCh) in the retina. 7KCh is a proinfl ammatory oxysterol known to be present in high amounts in oxidized LDL deposits associated with atheromatous plaques. 7KCh is generated in situ in these lipoprotein deposits where it can accumulate and reach very high concentrations. In normal primate retina, 7KCh has been found associated with lipoprotein deposits in the choriocapillaris, Bruch's membrane, and the retinal pigment epithelium (RPE). In photodamaged rats, 7KCh has been found in the neural retina in areas of high mitochondrial content, ganglion cells, photoreceptor inner segments and synapses, and the RPE. Intermediates found by LCMS indicate 7KCh is formed via a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via nuclear factor B and cause the induction of vascular endothelial growth factor, interleukin (IL)-6, and IL-8. There seems to be little evidence of 7KCh metabolism in the retina, although some form of effl ux mechanism may be active. The chronic mode of formation and the potent infl ammatory properties of 7KCh indicate it may be an "age-related" risk factor in aging diseases such as atherosclerosis, Alzheimer's, and age-related macular degeneration. -Rodríguez, I. R., and I. M. Larrayoz. Cholesterol oxidation in the retina: implications of 7-KCh formation in chronic infl ammation and age-related macular degeneration. J. Lipid Res . 2010. 51: 2847-2862. Supplementary key words 7-ketocholesterol • cytokines • oxysterolsIn the past year, numerous reviews have been published that extensively discuss the multiple functions of oxysterols and their complex relationships to diseases ( 1-7 ). However, the formation and function of oxysterols in the retina has not been well studied. Emerging studies are...

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“…Even though abundant data to supports the role of macrophages in LDL oxidation and the pathogenesis of atherosclerosis [21,22], it is unclear to what extent, the process of differentiation prepares macrophages for these roles, nor is it clear at what point the relevant genes are expressed. To obtain a more complete picture of this process, all genes identified in this biological process as undergoing a significant (> 2 fold, p < 0.05) change during monocyte to macrophage differentiation are presented in a heat map ( Figure 5).…”

Section: Lipid Fatty Acid and Steroid Processmentioning

confidence: 99%

Transcriptional diversity during monocyte to macrophage differentiation

et al. 2008

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Monocytes recruited into tissues from peripheral blood differentiate into macrophages, which are critical in the pathogenesis of many diseases. There is limited data concerning the global changes in the expression of genes during monocyte to macrophage differentiation, and how the patterns of change identify the mechanism contributing to macrophage differentiation or function. Employing microarray technology, we examined the transcriptional profile of in vitro adherence-induced differentiation of primary human monocytes into macrophages. We found the significant up regulation of genes contributing to the functions of macrophages, including those regulating to immunity and defense; lipid, fatty acid and steroid metabolism; cell adhesion, carbohydrate metabolism; amino acid metabolism and endocytosis. In contrast, the vast majority of transcription factors affected were down regulated during monocyte to macrophage differentiation, suggesting that transcriptional repression may be important for the transition from monocytes to macrophages. However, a limited number of transcription factors were up regulated, among these was C/EBPα, which may contribute to differentiation by regulating down stream genes, which are a characteristic of differentiated macrophages. These observations suggest that examination of the transcriptional profile in monocytes and macrophages in patients may identify relevant therapeutic targets in diseases mediated by macrophages.

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Oxidized lipoproteins and macrophages

Cited by 40 publications

References 82 publications

Oxysterols: A world to explore

Oxysterols: A world to explore

Cholesterol oxidation in the retina: implications of 7KCh formation in chronic inflammation and age-related macular degeneration

Transcriptional diversity during monocyte to macrophage differentiation

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