Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

Goulter, Andrew B.; Avella, Michael; Botham, Kathleen M.; Elliott, Jonathan

doi:10.1042/cs20030039

Cited by 13 publications

(10 citation statements)

References 42 publications

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“…Addition of oxidised CRLPs (oxCRLPs) to unstimulated vessels also raised vessel tone within minutes, suggesting these particles inhibit both agonist stimulation and tonic activity of the NO pathway, having an almost immediate effect (Fig. (1)) [80]. Further evidence for the inhibitory effect of oxCRLPs on basal activation of the NO pathway was provided by experiments involving cultured porcine aortic endothelial cells.…”

Section: Chylomicron Remnants and The Endo-theliummentioning

confidence: 95%

“…Further evidence for the inhibitory effect of oxCRLPs on basal activation of the NO pathway was provided by experiments involving cultured porcine aortic endothelial cells. Exposure of these cells to oxCRLPs reduced the rate of release of cGMP from these cells, a convenient measure of basal activity of the NO pathway [80].…”

Section: Chylomicron Remnants and The Endo-theliummentioning

confidence: 99%

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Direct Interaction of Dietary Lipids Carried in Chylomicron Remnants with Cells of the Artery Wall: Implications for Atherosclerosis Development

Botham¹,

Bravo²,

Elliott³

et al. 2005

CPD

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The development of atherosclerotic lesions in the artery wall is a complex process involving the endothelium, lipid engorged macrophages (foam cells) and smooth muscle cells. In recent years it has become clear that chylomicron remnants, the lipoproteins which carry lipids of dietary origin in the blood, are strongly atherogenic, and there is increasing evidence to indicate that this is due to direct interaction of the remnant particles with cells of the artery wall. Chylomicron remnants have been demonstrated to inhibit endothelium dependent vasorelaxation and to activate signal transduction pathways associated with inflammation in cultured endothelial cells. They have also been shown to be taken up by smooth muscle cells and macrophages, and to cause the extensive lipid accumulation associated with foam cell formation, as well as influencing the expression of key genes regulating macrophage lipid uptake and metabolism. Furthermore, oxidative modification of the remnant particles is not required for many of these effects. Chylomicron remnants, therefore, have multiple direct effects on three major cell types of the arterial wall which are likely to promote the development of atherosclerotic lesions. These effects may be modulated by various lipids carried by the particles, including the type of fat (saturated or unsaturated or oxidised fat), micronutrients such as vitamins and carotenoids which have antioxidant properties, and orally administered lipophilic drugs. Delayed clearance of chylomicron remnants from the blood occurs in a number of dyslipidemias associated with premature atherosclerosis development, and the potentially atherogenic effects of the particles would clearly be enhanced in these circumstances. Thus, elucidation of the mechanisms involved will aid in the identification of new drug targets which may be particularly useful for these conditions.

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Section: Chylomicron Remnants and The Endo-theliummentioning

confidence: 95%

Section: Chylomicron Remnants and The Endo-theliummentioning

confidence: 99%

Direct Interaction of Dietary Lipids Carried in Chylomicron Remnants with Cells of the Artery Wall: Implications for Atherosclerosis Development

Botham¹,

Bravo²,

Elliott³

et al. 2005

CPD

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show abstract

“…Other lipoproteins also have important effects on the bioavailablity of NO either by decreases biosynthesis or enhanced formation of superoxide. LDL, VLDL and chylomicron remnants have all been shown to have negative effects (Goulter et al, 2003;Takahashi et al, 2002), Fig. 7.…”

Section: Atherosclerosis and Hypercholesterolaemiamentioning

confidence: 98%

The role of nitric oxide in cardiovascular diseases

Naseem

2005

Molecular Aspects of Medicine

456

313

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“…Several pharmacological studies in rat and porcine vessels have now shown that CRLPs inhibit relaxation and potentiate vasoconstriction in an endothelium-dependent manner which is mediated, at least partly, by impaired generation of the vasodilator molecule NO (nitric oxide) [6,7]. Evidence that these particles also reduce basal NO production by cultured porcine ECs was subsequently provided [8].…”

Section: Cmrs (Chylomicron Remnants) and The Vessel Wallmentioning

confidence: 97%

Chylomicron remnants: mediators of endothelial dysfunction?

Wheeler‐Jones

2007

Biochemical Society Transactions

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Vascular disease is initiated by activation of the endothelium characterized by the predominance of pro-inflammatory and pro-coagulant changes in endothelial cells (ECs) referred to collectively as 'endothelial dysfunction'. There is increasing evidence that lipoproteins of dietary origin modulate EC function and the use of artificial chylomicron remnant-like particles (CRLPs) in vitro is now beginning to shed light on the molecular mechanisms through which these particles influence cell behaviour. CRLPs enriched in n-6 PUFAs (polyunsaturated fatty acids) influence the production of vasoactive mediators by ECs in a pro-inflammatory manner. Thus CRLPs reduce the synthesis and release of nitric oxide and alter the balance of release of vasodilator versus vasoconstrictor eicosanoids. These changes are accompanied by induction of cyclo-oxygenase-2 expression and activity as well as increased expression of adhesion molecules and the antioxidant defence enzyme haem oxygenase-1. CRLPs also activate a number of intracellular signalling pathways, including NF-kappaB (nuclear factor kappaB) and MAPKs (mitogen-activated protein kinases), which may be involved in mediating their effects on gene expression. The effects of CRLPs on EC behaviour can also be modulated by the type of fat/oxidation status of the particles. These findings support the hypothesis that lipoproteins of dietary origin directly regulate molecular events in the vascular wall.

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Chylomicron-remnant-like particles inhibit the basal nitric oxide pathway in porcine coronary artery and aortic endothelial cells

Cited by 13 publications

References 42 publications

Direct Interaction of Dietary Lipids Carried in Chylomicron Remnants with Cells of the Artery Wall: Implications for Atherosclerosis Development

Direct Interaction of Dietary Lipids Carried in Chylomicron Remnants with Cells of the Artery Wall: Implications for Atherosclerosis Development

The role of nitric oxide in cardiovascular diseases

Chylomicron remnants: mediators of endothelial dysfunction?

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