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

L Jonasson,H Grauen Larsen,A Schiopu,A A Bengtsson,A K Lundberg,B Gullstrand

doi:10.1038/s41598-017-17586-6

L Jonasson, H Grauen Larsen + Show 4 more

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https://doi.org/10.1038/s41598-017-17586-6

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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.

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Inflammation plays a central role in the development of cardiovascular disease (CVD)
The relative S100A8/A9 increase expressed as percent of baseline levels did not correlate with pre-stress S100A8/A9 (r = −0.114, p = 0.385) (Fig. 2b) or with the number of circulating neutrophils (Table 2), suggesting that the individual reactivity to psychological stress was independent of the habitual S100A8/A9 levels and of the neutrophil counts in blood
In this study we evaluated for the first time the stress-induced response of the pro-inflammatory alarmin S100A8/ A9 in humans

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Inflammation plays a central role in the development of cardiovascular disease (CVD). In ACS patients, S100A8/A9 levels are increased in blood and at the site of coronary occlusion, and recovered thrombi from coronary vessels contain S100A8/A9 positive cells[13] These findings suggest that S100A8/A9 is released locally from the ischemic myocardium and diffuses into the systemic circulation. CAD patients have a flat diurnal cortisol rhythm and a blunted cortisol response to acute stress, a cortisol pattern that is associated with elevated levels of pro-inflammatory markers[23]. S100A8/A9 is readily produced and stored in neutrophils and quickly released upon activation, serving as an ideal biomarker for monitoring rapid inflammatory responses It has not previously been studied whether acute psychological stress triggers S100A8/A9 release. We hypothesized that S100A8/A9 release is an integral part of the inflammatory response to stress, and that this response may be exacerbated in CAD patients with a dysregulated cortisol metabolism

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