Translational evidence of prothrombotic and inflammatory endothelial damage in Cushing Syndrome after remission

Abstract

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 to evaluate the subclinical cardiometabolic burden and to explore the direct proinflammatory 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. CS in remission (RCS); II. Active CS (ACS) and III. Controls (CTR), all matched for age, BMI, 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 (tisVCAM) and thrombogenicity of the generated extracellular matrix (ECM): von Willebrand Factor (VWF) and platelet reactivity.

Results

3 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<0.01). In vitro: EC exposed to ACS and RCS sera displayed increased tisVCAM-1 (p<0.01 for ACS and p<0.05 for RCS vs. CTR), VWF (p<0.01 for ACS and p<0.05 for RCS vs. CTR) and platelet adhesion on ECM (p<0.01 for ACC and p<0.05 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 proinflammatory endothelial effect that could increase cardiovascular risk.

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