The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt à NF-kappaB signalling pathways in human vascular endothelial cells

Schmidt, Annette; Geigenmüller, Sven; Buddecke, Eckhart

doi:10.1016/j.vph.2006.08.105

Cited by 12 publications

(16 citation statements)

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“…The activation of NF-B following exposure to extracellular proinflammatory stimuli results in the expression of several genes such as adhesion molecules in many cell types. HDL 3 reduce adhesion molecule expression in TNF-␣-treated cells in part by reducing NF-B activation, as demonstrated by other studies (20,61,62) and confirmed in the present work. Conversely, 15-LO-mediated modification significantly reduced the ability of HDL 3 to inhibit ROS formation and NF-B activation in TNF-␣-stimulated cells, suggesting a loss of anti-inflammatory activity in 15-LO-modified HDL 3 .…”

Section: Discussionsupporting

confidence: 91%

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

Pirillo

Uboldi

Bolego

et al. 2008

The Journal of Immunology

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Endothelial dysfunction represents one of the earliest events in vascular atherogenesis. Proinflammatory stimuli activate endothelial cells, resulting in an increased expression of adhesion molecules and chemoattractants that mediate leukocyte and monocyte adhesion, migration, and homing. High density lipoproteins (HDL) inhibit endothelial cell expression of adhesion molecules in response to proinflammatory stimuli. In the present work, we demonstrate that the modification of HDL3 (the major and the most antiatherogenic HDL subfraction) by 15-lipoxygenase (15-LO), an enzyme overexpressed in the atherosclerotic lesions, impairs the anti-inflammatory activity of this lipoprotein. The 15-LO-modified HDL3 failed to inhibit TNF-α-mediated mRNA and protein induction of adhesion molecules and MCP-1 in several models of human endothelial cells, and promoted inflammatory response by up-regulating the expression of such mediators of inflammation and by increasing monocyte adhesion to endothelial cells. Moreover, 15-LO-modified HDL3 were unable to contrast the formation of reactive oxygen species in cells incubated with TNF-α, and increased the reactive oxygen species content in unstimulated cells. Activation of NF-κB and AP-1 was mainly involved in the expression of adhesion molecules and MCP-1 induced by 15-LO-HDL3. Altogether, these results demonstrate that enzymatic modification induced by 15-LO impaired the protective role of HDL3, generating a dysfunctional lipoprotein endowed with proinflammatory characteristics.

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Section: Discussionsupporting

confidence: 91%

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

Pirillo

Uboldi

Bolego

et al. 2008

The Journal of Immunology

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“…Several reports suggest that SPC is the HDL component that mediates anti-inflammatory and antiatherogenic activity (25)(26)(27). SPC has also been shown to inhibit thrombin-induced NADPH oxidase-dependent CCL2 production from vascular smooth muscle cells (31), and TNF-a-induced expression of endothelial cell adhesion molecules such as E-selectin, ICAM-1, and VCAM-1 (32). In this study, to clearly understand the role of SPC in atherosclerosis, we used HUVECs to test the effects of SPC on the expression of CCL2, an important chemokine involved in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…In terms of the signaling events downstream of SPC stimulation in endothelial cells, previous reports demonstrated that SPC stimulates the calcium-, protein kinase C d-, and phospholipase D pathway leading to reactive oxygen species generation (34) and the ERK pathway resulting in apoptosis (35). The Akt and NF-kB pathways are also known act downstream of SPC stimulation (32). To gain insight into the intracellular signaling processes that lead to CCL2 production upon SPC stimulation of HUVECs, we tested for the activation of various signaling molecules.…”

Section: Discussionmentioning

confidence: 99%

Sphingosylphosphorylcholine Stimulates CCL2 Production from Human Umbilical Vein Endothelial Cells

Lee

Kim

et al. 2011

The Journal of Immunology

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Sphingosylphosphorylcholine (SPC) is a component of high-density lipoprotein particles. We investigated the functional role of SPC in HUVECs. SPC stimulation induced production of the CCL2 chemokine in a PTX-sensitive G-protein–dependent manner. SPC treatment caused the activation of NF-κB and AP-1, which are essential for SPC-induced CCL2 production, and induced the activation of three MAPKs, ERK, p38 MAPK, and JNK. Inhibition of p38 MAPK or JNK by specific inhibitors caused a dramatic decrease in SPC-induced CCL2 production. The Jak/STAT3 pathway was also activated upon SPC stimulation of HUVECs. Pretreatment with a Jak inhibitor blocked not only SPC-induced p38 MAPK and JNK activation, but also NF-κB and AP-1 activation. Our results suggest that SPC stimulates HUVECs, resulting in Jak/STAT3–, NF-κB–, and AP-1–mediated CCL2 production. We also observed that SPC stimulated expression of the adhesion molecule ICAM-1 in HUVECs. Our results suggest that SPC may contribute to atherosclerosis; therefore, SPC and its unidentified target receptor offer a starting point for the development of a treatment for atherosclerosis.

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“…In addition, HDL can deliver antioxidants such as vitamin E to cells [Mardones and Rigotti, 2004], and vitamin E has been shown to protect from OxLDL-induced cell death in endothelial cells [Vieira et al, 1998] and coronary smooth muscle cells [de Nigris et al, 2000]. Furthermore, several studies have demonstrated that HDL inhibit cell signaling mediated by OxLDL and thus offset several adverse biological effects [Suc et al, 1997;Robbesyn et al, 2003;Lee et al, 2005;Schmidt et al, 2006]. At the level of endothelium, it was demonstrated that the protective effect of HDL depends on stimulation of nitric oxide (NO) formation which regulates vasoreactivity [Rämet et al, 2003].…”

mentioning

confidence: 99%

HDL₃ reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: A protection against cell death

Brodeur

Brissette

Falstrault

et al. 2008

J of Cellular Biochemistry

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Oxidized low density lipoproteins (OxLDL) are known to promote atherosclerosis, but it is only recently that OxLDL have been associated with alterations of the functions of bone-forming osteoblasts and osteoporosis. Although high density lipoproteins (HDL) are recognized for their anti-atherogenic action, there is less information about their ability to protect against osteoporosis. Therefore, we investigated the capacity of HDL3 to prevent the cell death induced by OxLDL in human osteoblastic cells. Simultaneous exposure of the cells to HDL3 and OxLDL abolished the reduction of cell viability monitored by MTT activity measurement and the induction of apoptosis determined by annexin V staining indicating that HDL3 prevent the apoptosis of osteoblasts induced by OxLDL. This protection correlated with the displacement by HDL3 of OxLDL association to osteoblasts, signifying that OxLDL binding and/or internalization are/is necessary for their cytotoxic effects. We also found that exposition of osteoblastic cells to HDL3 prior to incubation with OxLDL reduced cell death and preserved the lysosomal integrity. This protection was correlated with an increase of SR-BI expression, a modification of OxLDL metabolism with less global uptake of OxLDL and greater selective uptake of cholesterol from OxLDL. These results strongly suggest that, as for atherosclerosis, HDL may exert beneficial actions on bone metabolism.

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The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt à NF-kappaB signalling pathways in human vascular endothelial cells

Cited by 12 publications

References 0 publications

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

Sphingosylphosphorylcholine Stimulates CCL2 Production from Human Umbilical Vein Endothelial Cells

HDL₃ reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: A protection against cell death

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The antiatherogenic and antiinflammatory effect of HDL-associated lysosphingolipids operates via Akt à NF-kappaB signalling pathways in human vascular endothelial cells

Cited by 12 publications

References 0 publications

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

The 15-Lipoxygenase-Modified High Density Lipoproteins 3 Fail to Inhibit the TNF-α-Induced Inflammatory Response in Human Endothelial Cells

Sphingosylphosphorylcholine Stimulates CCL2 Production from Human Umbilical Vein Endothelial Cells

HDL3 reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: A protection against cell death

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HDL₃ reduces the association and modulates the metabolism of oxidized LDL by osteoblastic cells: A protection against cell death