Glucocorticoid sensitivity and inflammatory status of peripheral blood mononuclear cells in patients with coronary artery disease. (3rd April 2018)

• Record Type: Journal Article
• Authors: Jönsson, Simon; Lundberg, Anna K.; Chung, Rosanna W. S.; Jonasson, Lena
• Is Part Of: Annals of medicine. Volume 50:Number 3(2018)
• Page Start: 260
• Page End: 268
• Publication Date: 2018-04-03
• Subjects: Coronary artery disease -- cortisol -- glucocorticoid -- glucocorticoid effect -- inflammation -- white blood cells; Medicine -- Periodicals; 610
• DOI: 10.1080/07853890.2018.1445278
• Languages: English
• ISSNs: 0785-3890

Abstract

Abstract: Objective: Mechanisms behind sustained inflammation in patients with coronary artery disease (CAD) are not clarified but hypothalamus-pituitary-adrenal (HPA) axis dysfunction may have a role. Here, we investigated whether inflammatory status of peripheral blood mononuclear cells (PBMCs) was associated with altered glucocorticoid sensitivity in CAD patients. Methods: In 55 CAD patients and 30 controls, mRNA levels of GR-α, GR-β, NF-κB, IκBα, MMP-9 and TIMP-1 were measured in PBMCs. Suppressive effects of dexamethasone on GR-α, GR-β, NF-κB, IκBα, MMP-9 and TIMP-1 mRNA levels were assessed in PBMCs ex vivo . Salivary cortisol was repeatedly measured over 3 days. Results: GR-α mRNA levels were higher in CAD patients than in controls, 0.50 (0.38–0.59) versus 0.26 (0.18–0.37), p < .001, while GR-β mRNA levels were equally low in both groups. GR-α mRNA expression was associated with inflammatory gene expression and, also, with flatter diurnal cortisol rhythm. In both patients and controls, dexamethasone suppressed gene expression of NF-κB, IκBα, MMP-9 and TIMP-1 ( p < .001). Dexamethasone also reduced GR-α mRNA levels ( p < .001), while LPS increased it ( p < .001). Conclusions: PBMCs from CAD patients displayed an inflammatory gene expression profile. This was not explained by reduced glucocorticoid sensitivity. Instead, inflammation was associated with increased expression of GR-α mRNA, suggesting a hypocortisolemic state. Key messages: Peripheral blood mononuclear cells from patients with coronary artery disease (CAD) display an inflammatory gene expression profile. This inflammatory state cannot be explained by reduced glucocorticoid sensitivity in CAD patients. Instead, the inflammatory gene expression profile is associated with upregulated levels of glucocorticoid receptor-α mRNA, suggesting a hypocortisolemic state.