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

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Bouillet, Benjamin | Gautier, Thomas | Denimal, Damien | Samson, Maxime | Masson, David | Pais de Barros, Jean Paul | Maquart, Guillaume | Xolin, Marion | Grosfeld, Alexandra | Dalle, Héloïse | Vergès, Bruno | Moldes, Marthe | Fève, Bruno

Edité par CCSD ; Oxford Univ. Press -

International audience. 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 HDL 2 -to-HDL 3 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.

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