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Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation

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Abstract

Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu2+, and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation (E max = 50.2 ± 5.0 vs 92.5 ± 1.7 % for incubation in Kreb’s buffer, p < 0.05) and native HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p < 0.05). At the opposite, oxidized HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.

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Acknowledgments

This study was supported by the Institut National de la Santé et de la Recherche Médicale and the Université de Bourgogne. None of them was implied in study design or data analysis or the decision to submit the article for publication.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculté de Médecine, INSERM U866-Université de Bourgogne, 21000, Dijon, France

    Laurence Perségol, Marie-Claude Brindisi, Serge Monier, Bruno Vergès & Laurence Duvillard

  2. Service d’Endocrinologie et Maladies Métaboliques, CHU, Hôpital du Bocage, 21000, Dijon, France

    Marie-Claude Brindisi & Bruno Vergès

  3. Plateforme Lipidomique, Structure Fédérative de Recherche, 21000, Dijon, France

    David Rageot & Jean-Paul Pais de Barros

  4. Biochimie Médicale, Plateau Technique de Biologie, 2 Rue Angélique Ducoudray, BP 37013, 21070, Dijon Cédex, France

    Laurence Duvillard

Authors
  1. Laurence Perségol
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  2. Marie-Claude Brindisi
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  3. David Rageot
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  4. Jean-Paul Pais de Barros
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  5. Serge Monier
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  6. Bruno Vergès
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  7. Laurence Duvillard
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Correspondence to Laurence Duvillard.

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Perségol, L., Brindisi, MC., Rageot, D. et al. Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation. Heart Vessels 30, 845–849 (2015). https://doi.org/10.1007/s00380-014-0543-2

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  • DOI: https://doi.org/10.1007/s00380-014-0543-2

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