Glucocorticoids impair HDL-mediated cholesterol efflux besides increased HDL cholesterol concentration: a proof of concept

in European Journal of Endocrinology
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  • 1 Department of Endocrinology, Diabetes and Metabolic Disorders, Dijon University Hospital, Dijon, France
  • 2 INSERM Unit, LNC-UMR 1231, University of Bourgogne Franche-Comté, Dijon, France
  • 3 Sorbonne University-INSERM, Saint-Antoine Research Center, UMR_S938, Institute of CardioMetabolism ICAN, Paris, France
  • 4 Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France
  • 5 INSERM, UMR1098, University of Bourgogne Franche-Comté, FHU, INCREASE, Dijon, France
  • 6 Department of Endocrinology, AP-HP Saint Antoine Hospital, Paris, France

Correspondence should be addressed to B Bouillet; Email: benjamin.bouillet@chu-dijon.fr
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Objective:

Glucocorticoids (GC) are associated with increased cardiovascular morbidity despite increased HDL-C concentration. HDL-mediated cholesterol efflux, a major anti-atherogenic property of HDL particles, is negatively associated with CVD risk. We aimed to determine whether HDL-mediated cholesterol efflux was influenced by GC.

Design:

Prospective, observational study.

Methods:

Lipid parameters, HDL composition, HDL-mediated cholesterol efflux, cholesteryl ester transfer protein, phospholipid transfer protein and lecithin cholesterol acyl-transferase (LCAT) activities were determined in ten patients with giant cell arteritis before and 3 months after GC introduction and in seven control subjects. HDL concentration and composition, HDL-mediated cholesterol efflux and LCAT activity were determined in GC-treated mice.

Results:

In patients, HDL-C concentration was higher after than before treatment GC-treatment (P = 0.002), while HDL-mediated cholesterol efflux was decreased (P = 0.008) and negatively associated with the proportion of cholesteryl ester in HDL (P = 0.04), independently of CRP. As well, in mice, HDL-C level was increased after GC exposure (P = 0.04) and HDL-mediated cholesterol efflux decreased (P = 0.04). GC-treated patients had higher cholesteryl ester content in HDL, higher HDL2-to-HDL3 ratio and higher LCAT activity than before treatment (P = 0.008, P = 0.02 and P = 0.004, respectively).

Conclusions:

We report, for the first time, that in patients with giant cell arteritis and mice treated with GC, HDL-mediated cholesterol efflux was impaired by GC besides an increased HDL-C level. This impaired HDL functionality, possibly related to HDL enrichment in cholesteryl ester, could contribute to the increased CVD risk observed in GC-treated patients. Further studies are needed in larger populations, to further decipher the effect of GC on HDL.

Supplementary Materials

    • Supplemental table 1. Relative composition of phospholipid and sphingolipid classes in HDL
    • Supplemental table 2. Correlations between intrinsic HDL-mediated cholesterol efflux and phospholipids and sphingolipids species in which distribution was changed under GC treatment
    • Supplemental Methods
    • Supplemental figure 1. Phospholipid and sphingolipid pattern of HDL in patients before GC treatment (white bars), after GC treatment (grey bars) and in control subjects (black bars).

 

     European Society of Endocrinology

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