Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol

Dugas, Bernard; Charbonnier, Sylvie; Baarine, Mauhamad; Ragot, Kévin; Delmas, Dominique; Ménétrier, Franck; Lherminier, Jeannine; Malvitte, L.; Khalfaoui, Taoufik; Bron, Alain M.; Creuzot‐Garcher, Catherine; Latruffe, Norbert; Lizard, Gérard

doi:10.1007/s00394-010-0102-2

Cited by 100 publications

(81 citation statements)

References 49 publications

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“…An interesting observation was that interstitial VEGF levels were lower (P ϭ 0.04 by paired t-test) in the nontraining group that had received resveratrol for 8 wk. This observation is in line with previous reports showing that resveratrol is able to reduce VEGF release from human endothelial and retinal cells in culture (10,63) and that resveratrol lowers hypoxia-induced VEGF release in human adipocytes (9). However, resveratrol did not seem to influence the amount of VEGF secreted during exercise, suggesting that the exercise-induced stimulus overruled the potential effect of resveratrol.…”

Section: Capillary-to-fiber Ratio and Vegfsupporting

confidence: 92%

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

Gliemann

Olesen

Biensø

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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modulates the angiogenic response to exercise training in skeletal muscles of aged men. Am J Physiol Heart Circ Physiol 307: H1111-H1119, 2014. First published August 15, 2014; doi:10.1152/ajpheart.00168.2014In animal studies, the polyphenol resveratrol has been shown to influence several pathways of importance for angiogenesis in skeletal muscle. The aim of the present study was to examine the angiogenic effect of resveratrol supplementation with parallel exercise training in aged men. Forty-three healthy physically inactive aged men (65 Ϯ 1 yr) were divided into 1) a training group that conducted 8 wk of intense exercise training where half of the subjects received a daily intake of either 250 mg trans-resveratrol (n ϭ 14) and the other half received placebo (n ϭ 13) and 2) a nontraining group that received either 250 mg trans-resveratrol (n ϭ 9) or placebo (n ϭ 7). The group that trained with placebo showed a ϳ20% increase in the capillary-to-fiber ratio, an increase in muscle protein expression of VEGF, VEGF receptor-2, and tissue inhibitor of matrix metalloproteinase (TIMP-1) but unaltered thrombospodin-1 levels. Muscle interstitial VEGF and thrombospodin-1 protein levels were unchanged after the training period. The group that trained with resveratrol supplementation did not show an increase in the capillary-to-fiber ratio or an increase in muscle VEGF protein. Muscle TIMP-1 protein levels were lower in the training and resveratrol group than in the training and placebo group. Both training groups showed an increase in forkhead box O1 protein. In nontraining groups, TIMP-1 protein was lower in the resveratrol-treated group than the placebo-treated group after 8 wk. In conclusion, these data show that exercise training has a strong angiogenic effect, whereas resveratrol supplementation may limit basal and training-induced angiogenesis.aging; antioxidant; physical activity; capillary; vascular endothelial growth factor SUFFICIENT O2 SUPPLY to the working skeletal muscle is vital to exercise performance, and the capillary network readily adapts according to demand in young healthy subjects (51). With advancing age, as with inactivity, the capillary supply to skeletal muscle decreases (7) and physical performance is reduced (66), eventually affecting activities of daily living and life quality (44,45). Acute physical activity increases the expression of various angiogenic factors in the skeletal muscle of both young and aged subjects (16,57,58), and, over weeks, regular physical activity leads to an increase in skeletal muscle capillarization (1,5,8).

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Section: Capillary-to-fiber Ratio and Vegfsupporting

confidence: 92%

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

Gliemann

Olesen

Biensø

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Lin reported that RSV protects against oxidized LDL-induced breakage of the blood-brain barrier . Limited evidence showed that RSV regulates VEGF level in vascular ECs; however, decreased VEGF level caused by RSV treatment was observed in gingival fibroblasts (Nunez et al 2010), retinal cells (Dugas et al 2010), tongue squamous cell carcinoma, and hepatoma cells (Zhang et al 2005). Based on these data, we hypothesized that RSV may regulate high-glucoseinduced hyperpermeability via VEGF pathway.…”

Section: Introductionmentioning

confidence: 83%

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Tian

Zhang

et al. 2012

Genes Nutr

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Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. b-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

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“…There is mounting evidence that treatment with 25-OHC and 7-ketoC up-regulates the production of a number of inflammatory mediators including IL-1a, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and MIP-1b in a wide variety of cell types (Prunet et al, 2006;Joffre et al, 2007;Morello et al, 2009;Dugas et al, 2010;Mascia et al, 2010). However, the mechanisms underlying the proinflammatory response to oxysterols remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The oxysterols 25-OHC and 7-ketoC have previously been shown to promote proinflammatory cytokine expression in non-gestational tissues at concentrations ranging from 0.8 to 30 mg/ml (Dugas et al, 2010;Palozza et al, 2010). Due to this variability amongst different cell types, we sought to test a variety of concentrations to assess their effects on inflammation in trophoblasts.…”

Section: -Ohc and 7-ketoc Promote Proinflammatory Cytokine Productimentioning

confidence: 99%

“…; MIP, macrophage inflammatory protein-1b; TNF-a, tumour necrosis factor-a. (Valenzuela et al, 2003), also induce inflammation in a variety of cell types (Dugas et al, 2010;Palozza et al, 2010), although the mechanism of cellular inflammatory activation is unclear. Oxidized LDL (oxLDL) particles which carry these oxysterols also produce proinflammatory effects which, at least in macrophages, may involve the activation of TLR2 and TLR4 (Chavez-Sanchez et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

Aye

Waddell

Mark

et al. 2012

Molecular Human Reproduction

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Oxidized cholesterol metabolites (oxysterols) promote inflammation in a variety of cell types and are thought to be involved in a number of disease pathologies. Oxysterol concentrations are increased in pregnancy, together with systemic oxidative stress and inflammation. We tested the hypothesis that oxysterols 25-hydroxycholesterol (25-OHC) and 7-ketocholesterol (7-ketoC) promote placental trophoblast inflammation, and determined the mechanisms involved. Treatment of primary trophoblasts in culture with 25-OHC and 7-ketoC increased the production of proinflammatory cytokines (interleukin-6, macrophage inflammatory protein-1b and tumour necrosis factor-a) in a concentration-dependent fashion. Inhibition of TLR4 activation using selective inhibitors of TLR4 complex formation (OxPAPC) or signalling transmission (CLI095) prevented lipopolysaccharide (LPS)-and oxysterol-induced inflammatory cytokine production. Pretreatment of trophoblasts with selective inhibitors of I-kB kinase activity (parthenolide and TPCA-1) reduced oxysterol-and LPS-stimulated inflammatory responses, consistent with the involvement of the nuclear factor kappa B (NF-kB) pathway downstream of TLR4 signalling. Both oxysterols also increased the phosphorylation and nuclear localization of NF-kB subunit p65/RelA. Oxysterols are also known to activate liver X receptors (LXRs) which can inhibit inflammatory signalling, either directly or indirectly via membrane cholesterol reduction. Treatment with the LXR agonist, T0901317, exerted significant anti-inflammatory effects, reducing LPS-and oxysteroldriven cytokine production. Treatment with methyl-b-cyclodextrin to deplete membrane microdomain cholesterol and thereby disrupt TLR4 signalling, similarly abrogated their effects. Together, these findings indicate that although oxysterols likely activate both pro-and anti-inflammatory pathways in the placenta, the predominant effect is the promotion of placental inflammation via TLR4-dependent activation of NF-kB.

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Effects of oxysterols on cell viability, inflammatory cytokines, VEGF, and reactive oxygen species production on human retinal cells: cytoprotective effects and prevention of VEGF secretion by resveratrol

Abstract: 7β-OH, 7KC, and 25-OH have cytotoxic, oxidative, inflammatory, and/or angiogenic activities on ARPE-19 cells. As Rsv has some protective effects against oxysterol-induced cell death and VEGF secretion it could be valuable in ARMD treatment.

Cited by 100 publications

References 49 publications

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

Resveratrol modulates the angiogenic response to exercise training in skeletal muscles of aged men

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway

Oxysterols exert proinflammatory effects in placental trophoblasts via TLR4-dependent, cholesterol-sensitive activation of NF- B

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