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Pro- or anti-inflammatory role of apolipoprotein A-1 in high-density lipoproteins?

von Eckardstein, Arnold
Published in Swiss Medical Weekly. 2013, vol. 143, p. w13781
Abstract Apolipoprotein A-1 (apoA-1) is the principal protein fraction of high-density lipoprotein (HDL), conferring to the latter many of its pleiotropic atheroprotective functions. After its effect on cholesterol efflux, the second most studied feature of apoA-1 is its anti-inflammatory property. In addition, it interferes with lipid peroxidation and innate immune receptors. These anti-inflammatory effects are due to various properties, in particular the ability to inhibit the transendothelial migration of immune cells by reducing integrin expression, to inhibit monocyte activation and cytokine production induced by T-cell contact, to inhibit lipid peroxidation and to interfere with innate immune receptors. Recent studies have demonstrated that during chronic systemic inflammation HDL could lose some of its atheroprotective functions and become dysfunctional or even proinflammatory. Recent evidence suggests that specific post-translational modifications of apoA-1 transform this genuine anti-inflammatory molecule into a proinflammatory one. The structural changes include chlorination, nitration and carbamylation of amino acids by myeloperoxidase, oxidation by reactive carbonyls, as well as glycation. Humoral autoimmunity to apoA-1 and HDL has been reported in populations at high cardiovascular risk and constitutes another emerging mechanism contributing to the loss of functions of apoA-1 and HDL. The fact that in recent trials cholesteryl ester transfer protein inhibitors (torcerapib and dalcetrapib) have unfortunately failed to prevent cardiovascular disease despite increasing cholesterol efflux in vitro and HDL levels in vivo, further highlights the clinical importance of understanding the mechanisms driving apoA-1 and HDL towards pro- or anti-inflammatory molecules. These findings should not affect current dyslipidaemia management guidelines.
Keywords Apolipoprotein A-I/immunology/metabolismAtherosclerosis/immunology/metabolismAutoimmunityHumansImmunity, InnateInflammationInflammation Mediators/immunologyLipoproteins, HDL/immunology
PMID: 23740387
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Article (Published version) (592 Kb) - public document Free access
Research groups Etude de l'activation des monocytes/macrophages et des polynucléaires neutrophiles (779)
Chimie et protéomique clinique (270)
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VUILLEUMIER, Nicolas et al. Pro- or anti-inflammatory role of apolipoprotein A-1 in high-density lipoproteins?. In: Swiss Medical Weekly, 2013, vol. 143, p. w13781. https://archive-ouverte.unige.ch/unige:42898

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Deposited on : 2014-12-09

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