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

Schmidt, Annette; Geigenmüller, Sven; Völker, Wolfgang; Buddecke, Eckhart

doi:10.1007/s00395-005-0582-z

Cited by 37 publications

(12 citation statements)

References 31 publications

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“…In addition to anti-atherosclerotic effects, HDL also has an anti-inflammatory role in macrophages and endothelial cells by inhibiting the expression of adhesion molecules (52,53). HDL activates Akt protein kinase to reduce the expression of E-selectin, intercellular cell adhesion molecule-1 and vascular cell adhesion protein 1, and thereby inhibits the function of tumor necrosis factor α to activate nuclear factor-κB in the nucleus, which has an anti-inflammatory role (54).…”

Section: The Function Of Hdlmentioning

confidence: 99%

High-density lipoprotein synthesis and metabolism (Review)

Zhou

Gao

et al. 2015

Molecular Medicine Reports

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High density lipoproteins (HDL) are heterogeneous particles regarding their size and composition. They have vital functions in reverse cholesterol transport (RCT). RCT occurs when lipid-free apolipoprotein AI recruits cholesterol and phospholipid to form nascent HDL particles. Adenosine triphosphate‑binding cassette transporters and scavenger receptor class B type I were found to be associated with the synthesis of HDL. Experimental studies have identified several potential anti‑atherogenic effects of HDL, including promotion of macrophage cholesterol outflow as well as anti‑inflammatory and anti‑thrombotic effects. HDL can also transport microRNAs. This review mainly summarizes the present knowledge of HDL synthesis and metabolism.

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Section: The Function Of Hdlmentioning

confidence: 99%

High-density lipoprotein synthesis and metabolism (Review)

Zhou

Gao

et al. 2015

Molecular Medicine Reports

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“…Inflammation and adhesion of mononuclear cells to the vascular wall are critical for AS initiation and development [36]. Inflammatory cytokines are important in the formation of lesional plaques and affect the entire atherosclerotic vessel [37].…”

Section: Resultsmentioning

confidence: 99%

CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury

Zhu

et al. 2016

PLoS ONE

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Endothelial dysfunction, which includes endothelial oxidative damage and vascular inflammation, is a key initiating step in the pathogenesis of atherosclerosis (AS) and an independent risk factor for this disorder. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation. In this study, we hypothesize that CLIC1 plays an important role in AS. Apolipoprotein E-deficient mice were supplied with a normal diet or a high-fat and high-cholesterol diet for 8 weeks. Overexpressed CLIC1 was associated with the accelerated atherosclerotic plaque development, amplified oxidative stress, and in vivo release of inflammatory cytokines. We subsequently examined the underlying molecular mechanisms through in vitro experiments. Treatment of cultured human umbilical vein endothelial cells (HUVECs) with H2O2 induced endothelial oxidative damage and enhanced CLIC1 expression. Suppressing CLIC1 expression through gene knocked-out (CLIC1−/−) or using the specific inhibitor indanyloxyacetic acid-94 (IAA94) reduced ROS production, increased SOD enzyme activity, and significantly decreased MDA level. CLIC1−/− HUVECs exhibited significantly reduced expression of TNF-α and IL-1β as well as ICAM-1 and VCAM-1 at the protein levels. In addition, H2O2 promoted CLIC1 translocation to the cell membrane and insertion into lipid membranes, whereas IAA94 inhibited CLIC1 membrane translocation induced by H2O2. By contrast, the majority of CLIC1 did not aggregate on the cell membrane in normal HUVECs, and this finding is consistent with the changes in cytoplasmic chloride ion concentration. This study demonstrates for the first time that CLIC1 is overexpressed during AS development both in vitro and in vivo and can regulate the accumulation of inflammatory cytokines and production of oxidative stress. Our results also highlight that deregulation of endothelial functions may be associated with the membrane translocation of CLIC1 and active chloride-selective ion channels in endothelial cells.

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“…SPC could also regulate the inflammation pathway in HUVECs. HDL-associated SPC had the ability to suppress the TNF-α-induced expression of endothelial cell E-selectin and the translocation of NF-κB into the cell nucleus [41]. This process was mediated through the activation of the PI3K/Akt pathway.…”

Section: Spc In Vesselsmentioning

confidence: 96%

“…Multiple studies in vitro have shown its pronounced influence on vessel pathology [40]. However, unlike S1P, many studies drew conflicting conclusions about the role of SPC in apoptosis and the inflammation of vessel cells [8,41]. Thus, whether SPC is beneficial or detrimental to atherosclerosis remains undetermined.…”

Section: Spc In Cardiovascular Disease Spc Relieves Myocardial Infarcmentioning

confidence: 99%

Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases

2018

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Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid in blood plasma that is metabolized from the hydrolysis of the membrane sphingolipid. SPC maintains low levels in the circulation under normal conditions, which makes studying its origin and action difficult. In recent years, however, it has been revealed that SPC may act as a first messenger through G protein-coupled receptors (S1P, GPR12) or membrane lipid rafts, or as a second messenger mediating intracellular Ca release in diverse human organ systems. SPC is a constituent of lipoproteins, and the activation of platelets promotes the release of SPC into blood, both implying a certain effect of SPC in modulating the pathological process of the heart and vessels. A line of evidence indeed confirms that SPC exerts a pronounced influence on the cardiovascular system through modulation of the functions of myocytes, vein endothelial cells, as well as vascular smooth muscle cells. In this review we summarize the current knowledge of the potential roles of SPC in the development of cardiovascular diseases and discuss the possible underlying mechanisms.

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

Cited by 37 publications

References 31 publications

High-density lipoprotein synthesis and metabolism (Review)

High-density lipoprotein synthesis and metabolism (Review)

CLIC1 Inhibition Attenuates Vascular Inflammation, Oxidative Stress, and Endothelial Injury

Emerging roles of sphingosylphosphorylcholine in modulating cardiovascular functions and diseases

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