High density lipoprotein-associated lysosphingolipids reduce E-selectin expression in human endothelial cells

Nofer, Jerzy–Roch; Geigenmüller, Sven; Göpfert, Christian; Assmann, Gerd; Buddecke, Eckhart; Schmidt, Annette

doi:10.1016/j.bbrc.2003.08.126

Cited by 67 publications

(43 citation statements)

References 21 publications

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“…Endothelial cells stimulated with TNF-show a dramatic increase in the levels of th adhesion molecule E-selectin; this activation is significantly reduced when cells are preincubated with HDL. A similar reduction in cell activation was found when cells were treated with either sphingosylphosphorylcholine or lysosulfatide, the two lysosphingolipids associated with HDL [161], suggesting that these HDL constituents may be responsible for this effect.…”

Section: Endothelial Cellssupporting

confidence: 57%

“…As stated above, there is convincing evidence that lipid-free apoA-I can mimic some of the actions of HDL. However, several studies suggest that HDL-associated lysosphingolipids are capable of inhibiting adhesion molecule expression on endothelial cells [160,161]. Endothelial cells stimulated with TNF-show a dramatic increase in the levels of th adhesion molecule E-selectin; this activation is significantly reduced when cells are preincubated with HDL.…”

Section: Endothelial Cellsmentioning

confidence: 99%

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High Density Lipoprotein: Assembly, Structure, Cargo, and Functions

Murphy

2013

ISRN Physiology

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Cardiovascular disease (CVD) is the leading cause of death globally. For close to four decades, we have known that high density lipoprotein (HDL) levels are inversely correlated with the risk of CVD. HDL is a complex particle that consists of proteins, phospholipids, and cholesterol and has the ability to carry micro-RNAs. HDL is constantly undergoing remodelling throughout its life-span and carries out many functions. This review summarizes many of the different aspects of HDL from its assembly, the receptors it interacts with, along with the functions it performs and how it can be altered in disease. While HDL is a key cholesterol efflux particle, this review highlights the many other important functions of HDL in the innate immune system and details the potential therapeutic uses of HDL outside of CVD.

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Section: Endothelial Cellssupporting

confidence: 57%

Section: Endothelial Cellsmentioning

confidence: 99%

High Density Lipoprotein: Assembly, Structure, Cargo, and Functions

Murphy

2013

ISRN Physiology

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“…Specific knockdown of SR-BI or S1P1 receptor by treatment of human endothelial cells with small interfering RNAs against SR-BI and PDZK1 or S1P1, respectively, markedly reduced the ability of HDLs to inhibit VCAM-1 expression and NF-κβ activation (Kimura et al 2006;Wu et al 2013), suggesting that both receptors may be critical for the anti-inflammatory endothelial actions of HDLs. Corresponding with the possible involvement of the S1P1 receptor, the inhibitory activity of HDLs on the expression of endothelial cell adhesion molecules has been proposed to be a function of biologically active lysosphingolipids carried by HDL particles (Nofer et al 2003;Kimura et al 2006). Besides the lipid component, the anti-inflammatory properties of HDLs could also be related to the microRNA content of HDL particles.…”

Section: Suppression Of Monocyte Extravasationmentioning

confidence: 99%

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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“…117 Lysosphingolipids present in HDLs, such as S1P, have been proposed as mediating the HDL-induced inhibition of VCAM-1 expression on endothelial cells. 118 However, despite considerable research in this area, the mechanisms underlying this anti-inflammatory effect of HDLs are still not completely understood. TNF-α enhances sphingosine kinase activity and the generation of S1P in endothelial cells, and this can be blocked by pre-incubation with HDL3.…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

High-Density Lipoproteins

Annema

Eckardstein

2013

Circ J

144

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Low plasma levels of high-density lipoprotein (HDL) cholesterol are associated with increased risks of coronary artery disease (CAD). HDL particles exert many effects in vitro and in vivo that may protect arteries from chemical or biological harm or facilitate repair of injuries. Nevertheless, HDL has not yet been successfully exploited for therapy. One potential reason for this shortfall is the structural and functional complexity of HDL particles, which carry more than 80 different proteins and more than 200 lipid species as well as several microRNAs and other potentially bioactive molecules. This physiological heterogeneity is further increased in several inflammatory conditions that increase cardiovascular risk, including CAD itself but also diabetes mellitus, chronic kidney disease, and rheumatic diseases. The quantitative and qualitative modifications of the proteome and lipidome, as well as the resulting loss of functions or gain of dysfunctions, are not recovered by the biomarker HDL-cholesterol. As yet the relative importance of the many physiological and pathological activities of normal and dysfunctional HDL, respectively, for the pathogenesis of atherosclerosis is unknown. The answer to this question, as well as detailed knowledge of structure-function-relationships of HDL-associated molecules, is a prerequisite to exploit HDL for the development of anti-atherogenic drugs as well as of diagnostic biomarkers for the identification, personalized treatment stratification, and monitoring of patients at increased cardiovascular risk. 2433Multifunctional but Vulnerable HDL munication of results. 15 As yet, clinical and epidemiological studies have come to discrepant and inconsistent conclusions on the prognostic performance of HDL subclasses differentiated by size. 14,20-24 Sometimes the associations of cardiovascular risk with the various HDL subclass concentrations were not stronger than with HDL-C, 20,21 and even if so, the associations with size were discrepant: significant associations with risk of cardiovascular events or stroke were found for small HDL in some studies, 22,23 but for medium-sized HDL 21,23 or large HDL 14,20,21,24 in others.Previous proteomic, lipidomic, and transcriptomic studies revealed a much greater structural complexity of HDLs: 80 different proteins, 25,26 more than 200 lipid species, 27,28 and several microRNAs 29,30 have been identified in HDL isolated from plasma by either ultracentrifugation, gel filtration, or immunoaffinity chromatography (Figure 1). Among the proteins, apoA-II is present in HDLs at the highest concentration after that of apoA-I and has been investigated for its cardiovascular risk association by several studies. In contrast to initial findings, large prospective studies did not find any significant differences in the risk association between apoA-II-containing and apoA-II-free HDL. [15][16][17] Despite their much lower concentrations relative to the 2 major proteins apoA-I and apoA-II and relative to the major lipids, many quantitatively minor componen...

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High density lipoprotein-associated lysosphingolipids reduce E-selectin expression in human endothelial cells

Cited by 67 publications

References 21 publications

High Density Lipoprotein: Assembly, Structure, Cargo, and Functions

High Density Lipoprotein: Assembly, Structure, Cargo, and Functions

HDL and Atherothrombotic Vascular Disease

High-Density Lipoproteins

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