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Translational evidence of prothrombotic and inflammatory endothelial damage in Cushing syndrome after remission
Author(s) -
Aranda Gloria,
FernandezRuiz Rebeca,
Palomo Marta,
Romo Mónica,
Mora Mireia,
Halperin Irene,
Casals Gregori,
Enseñat Joaquim,
Vidal Oscar,
DiazRicart Maribel,
Hanzu Felicia A.
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13521
Subject(s) - medicine , von willebrand factor , endothelial dysfunction , endocrinology , platelet , endothelium , platelet activation , in vivo , glucocorticoid , biology , microbiology and biotechnology
Summary Objective Sustained evidence from observational studies indicates that after remission of Cushing syndrome ( CS ) a cardiovascular risk phenotype persists. Here, we performed a translational study in active CS and CS in remission ( RCS ) to evaluate the subclinical cardiometabolic burden and to explore the direct pro‐inflammatory and prothrombotic potential of their sera on the endothelium in an in vitro translational atherothrombotic cell model. Patients Cross sectional study. The groups were (n = 9/group): I. RCS ; II . Active CS ( ACS ) and III . Controls ( CTR ), all matched for age, body mass index, sex, without other hormonal deficits. Design We evaluated in vivo: cardiometabolic profile; endothelial markers ( sVCAM ‐1, NO ); endothelial dysfunction ( FMD ); intima‐media thickness and body composition ( DEXA ). In vitro endothelial cells ( EC ) were exposed to sera taken from the different subjects to evaluate inflammatory EC response (tis VCAM ) and thrombogenicity of the generated extracellular matrix ( ECM ): von Willebrand factor ( VWF ) and platelet reactivity. Results Three of the 9 RCS subjects were on glucocorticoid replacement therapy ( GC ‐ RT ). Patients on GC ‐ RT had a shorter period of time in stable remission. In vivo analysis ACS showed typically metabolic features, while cardiometabolic markers reached statistical significance for RCS only for Hs‐ CRP ( P < .01). In vitro : EC exposed to ACS and RCS sera displayed increased tis VCAM ‐1 ( P < .01 for ACS and P < .05 for RCS vs CTR ), VWF ( P < .01 for ACS and P < .05 for RCS vs CTR ) and platelet adhesion on ECM ( P < .01 for ACC and P < .05 for RCS vs CTR ). No statistically significant differences were observed between GC ‐ RT RSC and RCS without GC ‐ RT . Conclusions The sera of premenopausal women with CS in remission, without atherothrombotic disease, contain circulatory endothelial deleterious factors with a direct thrombogenic and pro‐inflammatory endothelial effect that could increase cardiovascular risk.