Native and myeloperoxidase-oxidized low-density lipoproteins act in synergy to induce release of resolvin-D1 from endothelial cells

Damien Dufour, Alia Khalil, Vincent Nuyens, Alexandre Rousseau, Cédric Delporte, Caroline Noyon, Melissa Cortese, Florence Reyé, Valérie Pireaux, Jean Nève, Luc Vanhamme, Bernard Robaye, Christophe Lelubre, Jean Marc Desmet, Martine Raes, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen

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Abstract

Background and aims: Oxidation of native low-density lipoproteins (LDLs-nat) plays an important role in the development of atherosclerosis. A major player in LDL-nat oxidation is myeloperoxidase (MPO), a heme enzyme present in azurophil granules of neutrophils and monocytes. MPO produces oxidized LDLs called Mox-LDLs, which cause a pro-inflammatory response in human microvascular endothelial cells (HMEC), monocyte/macrophage activation and formation of foam cells. Resolvin D1 (RvD1) is a compound derived from the metabolism of the polyunsaturated fatty acid DHA, which promotes resolution of inflammation at the ng/ml level. Methods: In the present study, we used liquid chromatography–mass spectrometry (LC-MS/MS) to investigate the synthesis of RvD1 and its precursors - 17(S)-hydroxy docosahexaenoic acid (17S-HDHA) and docosahexaenoic acid (DHA) - by HMEC, in the presence of several concentrations of Mox-LDLs, copper-oxidized-LDLs (Ox-LDLs), and native LDLs or in mouse plasma. The LC-MS/MS method has been validated and applied to cell supernatants and plasma to measure production of RvD1 and its precursors in several conditions. Results: Mox-LDLs played a significant role in the synthesis of RvD1 and 17S-HDHA from DHA compared to Ox-LDLs. Moreover, Mox-LDLs and LDLs-nat acted in synergy to produce RvD1. In addition, different correlations were found between RvD1 and M1 macrophages, age of mice or Cl-Tyr/Tyr ratio. Conclusions: These results suggest that although Mox-LDLs are known to be pro-inflammatory and deleterious in the context of atherosclerosis, they are also able to induce a pro-resolution effect by induction of RvD1 from HMEC. Finally, our data also suggest that HMEC can produce RvD1 on their own.

Original languageEnglish
Pages (from-to)108-117
Number of pages10
JournalAtherosclerosis
Volume272
DOIs
Publication statusPublished - 1 May 2018

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Keywords

  • Atherosclerosis
  • Inflammation
  • Lipid mediators
  • Lipidomics
  • Low-density lipoproteins (LDLs)
  • Myeloperoxidase
  • Omega-3 fatty acids
  • Tandem mass spectrometry

Cite this

Dufour, D., Khalil, A., Nuyens, V., Rousseau, A., Delporte, C., Noyon, C., Cortese, M., Reyé, F., Pireaux, V., Nève, J., Vanhamme, L., Robaye, B., Lelubre, C., Desmet, J. M., Raes, M., Boudjeltia, K. Z., & Van Antwerpen, P. (2018). Native and myeloperoxidase-oxidized low-density lipoproteins act in synergy to induce release of resolvin-D1 from endothelial cells. Atherosclerosis, 272, 108-117. https://doi.org/10.1016/j.atherosclerosis.2018.03.012