Stress-induced release of the S100A8/A9 alarmin is elevated in coronary artery disease patients with impaired cortisol response

Abstract

Psychological stress is thought to be an important trigger of cardiovascular events, yet the involved pathways and mediators are largely unknown. Elevated systemic levels of the pro-inflammatory alarmin S100A8/A9 correlate with poor prognosis in coronary artery disease (CAD) patients. Here, we investigated the links between S100A8/A9 release and parameters of anti-inflammatory glucocorticoid secretion in two different cohorts subjected to a psychological stress test. In the first cohort of 60 CAD patients, psychological stress induced a rapid increase of circulating S100A8/A9. This rapid S100A8/A9 response strongly correlated with elevated evening saliva cortisol levels, suggesting an association with a dysregulated hypothalamic–pituitary–adrenal (HPA) axis. In the second cohort of 27 CAD patients and 28 controls, elevated S100A8/A9 levels were still detectable 24 h after stress in 40% of patients and 36% of controls, with a tendency for higher levels in patients. The sustained S100A8/A9 response was associated with a poor rapid cortisol release after stress in patients, but not in the control group. Our findings reveal for the first time that acute psychological stress induces elevated levels of S100A8/A9. We also provide hypothesis-generating evidence that dysregulated cortisol secretion in CAD patients might be associated with an exaggerated pro-inflammatory S100A8/A9 response.

Relationships Between Serum Cortisol, RAGE-Associated s100A8/A9 Levels, and Self-Reported Cancer-Related Distress in Women With Nonmetastatic Breast Cancer

“…Similarly, there was variation in cortisol and s100A8/A9 levels. Mean levels of s100A8/A9 in this study, as expected, were greater than mean levels in prior reports with noncancer samples (42,43) and lower than mean levels in nonmetastatic BCa patients with high distress (39) and patients with metastatic BCa (40). It would be valuable in a future study to determine if a significant relationship would emerge between distress and s100A8/A9 in a distressed sample.…”

Low social and family well-being is associated with greater RAGE ligand s100A8/A9 and interleukin-1 beta levels in metastatic breast cancer patients

“…The measurement of S100 proteins and IL-1β in saliva has been considered a valid and reliable method ( Idris et al., 2015 ; Janigro et al., 2020 ; Jonasson et al., 2017 ; Karna et al., 2019 ; Spiekermann et al., 2017 ) and IL-1β is more detectable in saliva than in blood serum ( Idris et al., 2015 ). In the present study, unstimulated whole saliva was self-collected by each patient over 2 consecutive days at 5pm with untreated Salivettes®, as described by the manufacturer (Sarstedt AG & Co. KG, 51588 ​Nümbrecht, Germany).…”

Identification and analysis of chemokine-related and NETosis-related genes in acute pancreatitis to develop a predictive model

“…Through immunocytochemistry, Sprenkeler EGG et al found S100A8/A9 in NETs and demonstrated that it was released simultaneously with DNA during NETosis ( Sprenkeler et al, 2022 ). Activated neutrophils immediately release S100A8/A9 upon activation, making it an ideal biomarker for rapid inflammatory responses ( Jonasson et al, 2017 ). S100A8/A9 was significantly increased in exosomes from SAP and activated NADPH oxidase, producing free radicals and promoting inflammatory response ( Carrascal et al, 2022 ).…”