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Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherogenesis

Chylomicron remnants: mediators of endothelial dysfunction?

C.P.D. Wheeler-Jones
Biochemical Society Transactions Jun 01, 2007, 35 (3) 442-445; DOI: 10.1042/BST0350442
C.P.D. Wheeler-Jones
Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
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Abstract

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-κB (nuclear factor κB) 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.

  • chylomicron remnant-like particle
  • cyclo-oxygenase (COX)
  • endothelial cell
  • haem oxygenase-1 (HO-1)
  • mitogen-activated protein kinase (MAPK)
  • prostanoid

Footnotes

  • Diet and Cardiovascular Health: Chylomicron Remnants and Their Emerging Roles in Vascular Dysfunction in Atherogenesis: Biochemical Society Focused Meeting held at The Royal Veterinary College, London, U.K., 18–19 December 2006. Organized and Edited by K. Botham and C. Wheeler-Jones (Royal Veterinary College, London, U.K.).

Abbreviations: CM, chylomicron; COX-2, cyclo-oxygenase-2; CMR, chylomicron remnant; CRLP, CMR-like particle; DCF, 2′,7′-dichlorofluorescin; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; ERK1/2, extracellular-signal-regulated kinase 1/2; HO-1, haem oxygenase-1; HUVEC, human umbilical vein EC; MAPK, mitogen-activated protein kinase; MUFA, mono-unsaturated fatty acid; NF-κB, nuclear factor κB; PGI2, prostacyclin (prostaglandin I2); PGIS, prostacyclin synthase; PUFA, polyunstaurated fatty acid; RLP, remnant-like particle; ROS, reactive oxygen species; SFA, saturated fatty acid; TAG, triacylglycerol; Tx, thromboxane; VSMC, vascular smooth muscle cell

  • © 2007 Biochemical Society
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June 2007

Volume: 35 Issue: 3

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Chylomicron remnants: mediators of endothelial dysfunction?
C.P.D. Wheeler-Jones
Biochemical Society Transactions Jun 2007, 35 (3) 442-445; DOI: 10.1042/BST0350442
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Chylomicron remnants: mediators of endothelial dysfunction?
C.P.D. Wheeler-Jones
Biochemical Society Transactions Jun 2007, 35 (3) 442-445; DOI: 10.1042/BST0350442

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  • Article
    • Abstract
    • CMRs (chylomicron remnants) and the vessel wall
    • Effects of CRLPs on cultured endothelial and VSMCs (vascular smooth muscle cells)
    • Activation of signalling pathways by CRLPs
    • CRLPs and vascular protection?
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Keywords

chylomicron remnant-like particle
cyclo-oxygenase (COX)
endothelial cell
haem oxygenase-1 (HO-1)
mitogen-activated protein kinase (MAPK)
prostanoid

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