High-Density Lipoproteins Differentially Modulate Cytokine-Induced Expression of E-Selectin and Cyclooxygenase-2

Cockerill, Gillian; Saklatvala, Jeremy; Ridley, Simon H.; Yarwood, Helen; Miller, N. E.; Oral, Barbaros; Nithyanathan, Saro; Taylor, Graham W.; Haskard, Dorian O.

doi:10.1161/01.atv.19.4.910

Cited by 116 publications

(73 citation statements)

References 70 publications

(57 reference statements)

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“…Because HDLs do not inhibit IB␣ degradation or the nuclear translocation of nuclear factor-B, the mechanism must involve a process independent of this ubiquitous family of transactivating factors. 27 In summary, we have shown for the first time that elevation of the circulating level of HDLs, in a genetically normal large mammal, can inhibit cytokine adhesion molecule expression in vivo. Our data support the anti-inflammatory function of HDLs as a potential mechanism for the recent demonstration that recA-I Milano particles reduce macrophage infiltration in lesions in apoE-null mice, 51 a mechanism further supported by the recent demonstration that recHDLs were also able to inhibit neointimal thickening and VCAM-1 expression in the same mouse model.…”

Section: Concentration Of Human Apo A-i In Pig Plasma After a Bolus Imentioning

confidence: 74%

“…HDLs were found to inhibit the upregulation of E-selectin, VCAM-1, and ICAM-1 by interleukin (IL)-1␤ or tumor necrosis factor-␣ in cultured human umbilical vein endothelial cells at the level of both steady-state mRNA and surface protein expression. 26,27 In the present study, we used a radiolabeled monoclonal antibody targeting technique in the pig, developed in our laboratory, 28 -30 to show that inhibition of E-selectin expression by HDLs also occurs in vivo. DLs) were prepared from plasma-derived human apoA-I and soybean phosphatidylcholine by cholate dialysis in the ZLB Central Laboratory, 31,32 resulting in the generation of discoidal particles with an average protein:phospholipid molar ratio of 1:150.…”

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confidence: 99%

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Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation

et al. 2001

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Background-Although there is strong evidence that plasma HDL levels correlate inversely with the incidence of coronary artery disease, the precise mechanism(s) for the protective effect of HDLs remains unclear. We recently showed that HDLs inhibit endothelial cell expression of cytokine-induced leukocyte adhesion molecules in vitro. Our study therefore sought to test the hypothesis that elevating the level of circulating HDLs would inhibit endothelial cell activation in vivo. Methods and Results-We used a porcine model of inflammation previously established in our laboratory, in which the level of vascular endothelial cell expression of E-selectin in interleukin (IL)-1␣-induced skin lesions was measured by the uptake of a radiolabeled anti-E-selectin antibody (1.2B6). Porcine plasma HDL levels were elevated by use of a bolus injection of reconstituted discoidal HDL (recHDL). These particles resemble nascent HDL particles in shape and contain apolipoprotein A-I as the sole protein and soybean phosphatidylcholine as the sole phospholipid. We found that recHDLs inhibited the expression of IL-1␣-induced E-selectin by porcine aortic endothelial cells in vitro, confirming that the inhibitory effect is conserved with synthetic HDLs and demonstrating that the phenomenon is not restricted to human endothelial cells. In vivo, elevating the circulating level of HDLs Ϸ2-fold led to significant inhibition of basal and IL-1␣-induced E-selectin expression by porcine microvascular endothelial cells. Conclusions-These observations demonstrate the potential anti-inflammatory action of HDLs and provide support for the further investigation of the mechanisms underlying the inhibitory effects of HDLs on endothelial cell activation.

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Section: Concentration Of Human Apo A-i In Pig Plasma After a Bolus Imentioning

confidence: 74%

mentioning

confidence: 99%

Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation

et al. 2001

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“…At least part of the resistance to atherosclerosis induced by cluster expression could have been attributable to properties of HDLs unrelated to their role in RCT, such as their ability to protect LDLs from oxidative modification 31 or to suppress adhesion molecule expression and induce cyclooxygenase-2 in vascular endothelium. 32 Associated changes in the concentration, size, and composition of apoBcontaining lipoproteins may also have contributed. Further work will be needed to clarify the mechanism(s) of the antiatherogenic effect of human cluster expression in mice.…”

Section: Vergnes Et Al Human Apoa-i/c-iii/a-iv Cluster Tg Micementioning

confidence: 99%

Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Vergnes

Baroukh

Ostos

et al. 2000

ATVB

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Abstract-The apolipoprotein (apo)A-I/C-III/A-IV gene cluster is involved in lipid metabolism and atherosclerosis.Overexpression of apoC-III in mice causes hypertriglyceridemia and induces atherogenesis, whereas overexpression of apoA-I or apoA-IV increases cholesterol in plasma high density lipoprotein (HDL) and protects against atherosclerosis. Each gene has been studied alone in transgenic mice but not in combination as the entire cluster. To determine which phenotype is produced by the expression of the entire gene cluster, transgenic mice were generated with a 33-kb human DNA fragment. The results showed that the transgene contained the necessary elements to direct hepatic and intestinal expression of the 3 genes. In the pooled data, plasma concentrations were 257Ϯ9, 7.1Ϯ0.5, and 1.0Ϯ0.2 mg/dL for human apoA-I, apoC-III, and apoA-IV, respectively (meanϮSEM). Concentrations of these apolipoproteins were higher in males than in females. Human apoA-I and apoC-III concentrations were positively correlated, suggesting that they are coregulated. Transgenic mice exhibited gross hypertriglyceridemia and accumulation of apoB 48 -containing triglyceride-rich lipoproteins. Plasma triglyceride and cholesterol concentrations were correlated positively with human apoC-III concentration, and HDL cholesterol was correlated with apoA-I concentration. In an apoE-deficient background, despite being markedly hypertriglyceridemic, cluster transgenic animals compared with nontransgenic animals showed a 61% reduction in atherosclerosis. This suggests that apoA-I and/or apoA-IV can protect against atherosclerosis even in the presence of severe hyperlipidemia. These mice provide a new model for studies of the regulation of the 3 human genes in combination. Key Words: transgenic mice Ⅲ hypertriglyceridemia Ⅲ cholesterol Ⅲ lipoproteins Ⅲ atherosclerosis P lasma lipoproteins influence the development of atherosclerosis, and their concentrations are associated with the risk of coronary heart disease. 1 The genes for 3 apolipoproteins, apoA-I, apoC-III, and apoA-IV, are grouped together in a cluster on 17 kb of human chromosome 11. 2 ApoA-I is the major protein component of HDL. Through its ability to promote cholesterol efflux from cultured cells and to activate lecithin:cholesterol acyltransferase (LCAT), it is involved in reverse cholesterol transport (RCT). 1 Expression of the human apoA-I ( h apoA-I) gene decreases the development of fatty lesions in cholesterol-fed transgenic (Tg) mice 3 and in apoE-deficient (apoE Ϫ/Ϫ ) mice. 4 ApoA-I deficiency in mice did not increase atherogenesis in a normal background 5 but did so in hypercholesterolemic mice expressing human apoB. 6 ApoC-III is a component of HDL and triglyceride-rich lipoproteins (TGRLs). Plasma apoC-III concentration is positively correlated with triglyceride concentration. By inhibiting TGRL catabolism, apoC-III induces hypertriglyceridemia in Tg mice. 7 Expression of the gene was not atherogenic in apoE Ϫ/Ϫ mice. 8 In contrast, h apoC-III expression, in normal or in LDL ...

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Section: Mechanism By Which Hdls Inhibit Adhesion Molecule Expressionmentioning

confidence: 99%

“…99 The ability of HDL to inhibit the nuclear translocation of NF-b has been confirmed by one group, 98 although another report concluded that an HDL-mediated inhibition of E-selectin is independent of NK-b. 107 The explanation for this discrepancy is unclear and will have to await further research.Oxidized forms of HDL may activate NF-b and promote its nuclear translocation in a process that is linked to an increase in the generation of intracellular reactive oxygen species. 108 A reduction in the activation of NF-b may be secondary to a reduction in oxidative stress.…”

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confidence: 99%

Anti-Inflammatory Properties of HDL

Ansell

Navab

Watson

et al. 2004

Rev Endocr Metab Disord

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Abstract-There are several well-documented functions of high-density lipoprotein (HDL) that may explain the ability of these lipoproteins to protect against atherosclerosis. The best recognized of these is the ability of HDL to promote the efflux of cholesterol from cells. This process may minimize the accumulation of foam cells in the artery wall. However, HDL has additional properties that may also be antiatherogenic. For example, HDL is an effective antioxidants. The major proteins of HDL, apoA-I and apoA-II, as well as other proteins such as paraoxonase that cotransport with HDL in plasma, are well-known to have antioxidant properties. As a consequence, HDL has the capacity to inhibit the oxidative modification of low-density lipoprotein (LDL) in a process that reduces the atherogenicity of these lipoproteins. HDL also possesses other antiinflammatory properties. By virtue of their ability to inhibit the expression of adhesion molecules in endothelial cells, they reduce the recruitment of blood monocytes into the artery wall. These antioxidant and antiinflammatory properties of HDL may be as important as its cholesterol efflux function in terms of protecting against the development of atherosclerosis. Key Words: antiinflammatory Ⅲ antioxidant Ⅲ atherosclerosis Ⅲ high-density lipoprotein I n epidemiological studies, high plasma levels of highdensity lipoproteins (HDLs) protect against the development of atherosclerosis. 1,2 The precise mechanism is uncertain, although most likely it is the consequence of one or more of the reported actions of HDL. 3 The best known of these relates to the ability of HDL to promote the efflux of cholesterol from cells in the artery wall. 4 However, HDLs have additional functions, some of which may be unrelated to their role in plasma lipid transport. For example, they bind lipopolysaccharide, 5 stimulate endothelial cell movement, 6 inhibit the synthesis of plateletactivating factor by endothelial cells, 7 and protect erythrocytes against the generation of procoagulant activity. 8 HDLs stimulate prostacyclin synthesis by endothelial cells. 9 They also bind prostacyclin and thus prolong its half-life. 10 They reduce epidermal growth factor-induced DNA synthesis in vascular smooth muscle cells. 11 HDLs are antithrombotic. 12 They modulate endothelial function, 13 probably by stimulating endothelial nitric oxide (NO) production. 14 HDLs also possess antioxidant and antiinflammatory activities. 3,[15][16][17][18][19][20][21] The degree to which any or all of these nonlipid transport functions of HDL contribute to a protection against atherosclerosis is still uncertain, although evidence is mounting that at least some of them may be especially important.This review focuses on the antioxidant and antiinflammatory properties of HDL (Figure 1). It summarizes the role of oxidation and inflammation in atherogenesis and describes how these processes may be inhibited by HDL. It concludes with an assessment of the potential clinical importance of the antioxidant and antiinflammatory propert...

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High-Density Lipoproteins Differentially Modulate Cytokine-Induced Expression of E-Selectin and Cyclooxygenase-2

Cited by 116 publications

References 70 publications

Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation

Elevation of Plasma High-Density Lipoprotein Concentration Reduces Interleukin-1–Induced Expression of E-Selectin in an In Vivo Model of Acute Inflammation

Expression of Human Apolipoprotein A-I/C-III/A-IV Gene Cluster in Mice Induces Hyperlipidemia but Reduces Atherogenesis

Anti-Inflammatory Properties of HDL

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