HDL counterbalance the proinflammatory effect of oxidized LDL by inhibiting intracellular reactive oxygen species rise, proteasome activation, and subsequent NF‐κB activation in smooth muscle cells

Robbesyn, Fanny; Garcia, Virginie; Augé, Nathalie; Vieira, Otília V.; Frisach, Marie-Françoise; Salvayre, Robert; Negre-Salvayre, Anne

doi:10.1096/fj.02-0240fje

Cited by 97 publications

(81 citation statements)

References 54 publications

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“…14,31 The upstream mechanisms and potential targets of HDLs involved in Ca 2 þ deregulation are still unknown. However, the antioxidant properties of HDLs that inhibit intracellular oxidative stress mediated by oxLDLs, 20 could explain their protective effect, as oxidative stress is a well-known inducer of ER stress and calcium deregulation 9,39 In conclusion, our data show a potent implication of ER stress and CHOP in apoptosis mediated by oxLDLs in vascular cells, resulting from the deregulation of cytosolic Ca 2 þ . These results also point out that the oxLDLs-induced ER stress is associated to autophagy activation, which is not involved in oxLDLs-mediated cell death machinery, but may contribute to PS exposure and subsequent phagocytosis of oxLDLs exposed cells.…”

Section: Discussionmentioning

confidence: 69%

“…18 HDLs inhibit LDLs oxidation, and counteract several adverse biological effects, such as cytotoxicity and inflammatory response triggered by cytokines, oxLDLs or oxidants. 18,19 HDLs counterbalance the proinflammatory effect of oxLDLs by inhibiting intracellular reactive oxygen species rise and subsequent NF-kB activation in vascular cells, 20 and by preventing the formation of oxLDLs-induced carbonyl-protein adducts. 8 Recently, the anti-inflammatory role of HDLs has been linked to a reduced induction of ER stress elicited by oxidized phospholipids, including the expression of ATF-3, ATF-4 and spliced XBP1 genes.…”

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confidence: 99%

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HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

et al. 2010

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The apoptotic effect of oxidized LDLs (oxLDLs) is mediated through a complex sequence of signaling events involving a deregulation of the cytosolic Ca 2 þ homeostasis. OxLDLs also trigger ER stress that may lead to cellular dysfunction and apoptosis, through the activation of the IRE1a/c-Jun N-terminal kinase pathway. Moreover, ER stress and oxidized lipids have been shown to trigger autophagy. The antiatherogenic high-density lipoproteins (HDLs) display protective effects against oxLDLs toxicity. To more deeply investigate the mechanisms mediating the protective effects of HDLs, we examined whether ER stress and autophagy were implicated in oxLDLs-induced apoptosis and whether HDLs prevented these stress processes. We report that, in human endothelial cells, HDLs prevent the oxLDL-induced activation of the ER stress sensors IRE1a, eIF2a and ATF6 and subsequent activation of the proapoptotic mediators JNK and CHOP. OxLDLs also trigger the activation of autophagy, as assessed by LC3 processing and Beclin-1 expression. The autophagic process is independent of the proapoptotic arms of ER stress, but Beclin-1 contributes to PS exposure and subsequent phagocytosis of oxLDLs exposed cells. Induction of autophagy and PS exposure by oxLDLs is prevented by HDLs. Finally, the cytosolic Ca 2 þ deregulation triggered by oxLDLs is a common signaling pathway that mediates ER stress-induced cell death and autophagy, all these events being blocked by HDLs.

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Section: Discussionmentioning

confidence: 69%

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confidence: 99%

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

et al. 2010

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“…Finally, HDLs were found to suppress inflammatory responses in VSMCs. Oxidized LDLs, via formation of ROS, induced NF-κβ activation in cultured VSMCs, while their pretreatment with HDLs inhibited the intracellular rise in ROS and the subsequent upregulation of NF-κβ elicited by the oxidized LDLs (Robbesyn et al 2003).…”

Section: Effects Of Hdls On Smooth Muscle Cellsmentioning

confidence: 95%

HDL and Atherothrombotic Vascular Disease

Annema

Eckardstein

Kovanen

2014

High Density Lipoproteins

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High-density lipoproteins (HDLs) exert many beneficial effects which may help to protect against the development or progression of atherosclerosis or even facilitate lesion regression. These activities include promoting cellular cholesterol efflux, protecting low-density lipoproteins (LDLs) from modification, preserving endothelial function, as well as anti-inflammatory and antithrombotic effects. However, questions remain about the relative importance of these activities for atheroprotection. Furthermore, the many molecules (both lipids and proteins) associated with HDLs exert both distinct and overlapping activities, which may be compromised by inflammatory conditions, resulting in either loss of function or even gain of dysfunction. This complexity of HDL functionality has so far precluded elucidation of distinct structure-function relationships for HDL or its components. A better understanding of HDL metabolism and structure-function relationships is therefore crucial to exploit HDLs and its associated components and cellular pathways as potential targets for anti-atherosclerotic therapies and diagnostic markers.

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“…The fact that antioxidants prevented the oxLDL-dependent changes in promoter activity also supports a role for reactive oxygen species in the genesis of the observed effects. Reactive oxygen species and NF-kB seem also to play a role in the regulation of cell function by oxLDL in other pathophysiological conditions (7,44).…”

Section: Discussionmentioning

confidence: 99%

Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins

Martínez-Miguel

Raoch

Zaragoza

et al. 2009

Journal of Lipid Research

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The aim of our study was to analyze the relationships between atherosclerosis and endothelin-converting enzyme-1 (ECE-1). Four-week-old C57BL/6J [wild-type (WT)] and apolipoprotein E-deficient (apoE) mice were fed with a standard or Western-type fat diet for 8 wks. ApoE showed atherosclerotic lesions in the aorta, higher blood pressure and vascular lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) protein content than WT. ApoE showed a significant increase in ECE-1 protein content and mRNA expression in aorta, lung, and kidney, without changes in heart. When an ECE-1 inhibitor, FR-901533, was administered to them, blood pressure decreased in apoE on fat diet versus apoE on normal diet and WT. ECE-1 and LOX-1 protein content were elevated in peripheral blood mononuclear cells (PBMC) from hypercholesterolemic patients. In order to study the mechanism involved in this ECE-1 up-regulation, bovine aortic endothelial cells (BAEC) were treated with oxidized-low density lipoproteins (oxLDL). OxLDL, but not LDL, increased ECE-1 protein content, mRNA expression and promoter activity. Our results demonstrate that ECE-1 increases in different atherosclerosis situations. Up-regulation of ECE-1 could contribute, at least partially, to the development of hypertension seen in apoE mice, because FR-901533 avoided it. Probably, atherosclerotic situations course with an increase of oxLDL, which is able to induce ECE-1 expression with the subsequent potential pathological effects.-Martínez-Miguel, P., V. Raoch, C. Zaragoza, J. M. Valdivielso, M. Rodríguez-Puyol, D. Rodríguez-Puyol, and S. López-Ongil. Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins. J. Lipid Res. 2009. 50: 364-375.

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HDL counterbalance the proinflammatory effect of oxidized LDL by inhibiting intracellular reactive oxygen species rise, proteasome activation, and subsequent NF‐κB activation in smooth muscle cells

Cited by 97 publications

References 54 publications

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

HDL and Atherothrombotic Vascular Disease

Endothelin-converting enzyme-1 increases in atherosclerotic mice: potential role of oxidized low density lipoproteins

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