AIMS: Mental stress substantially contributes to the initiation and progression of human disease, including cardiovascular conditions. We aim to investigate the underlying mechanisms of these contributions since they remain largely unclear. METHODS AND RESULTS : Here, we show in humans and mice that leucocytes deplete rapidly from the blood after a single episode of acute mental stress. Using cell-tracking experiments in animal models of acute mental stress, we found that stress exposure leads to prompt uptake of inflammatory leucocytes from the blood to distinct tissues including heart, lung, skin, and, if present, atherosclerotic plaques. Mechanistically, we found that acute stress enhances leucocyte influx into mouse atherosclerotic plaques by modulating endothelial cells. Specifically, acute stress increases adhesion molecule expression and chemokine release through locally derived norepinephrine. Either chemical or surgical disruption of norepinephrine signalling diminished stress-induced leucocyte migration into mouse atherosclerotic plaques. CONCLUSION : Our data show that acute mental stress rapidly amplifies inflammatory leucocyte expansion inside mouse atherosclerotic lesions and promotes plaque vulnerability.
FörderungenGerman Research Foundation (HI1573/2) European Research Council AdG°692511, DFG SFB1123-A1/A10/Z1 and TRR267-B02 German Federal Ministry of Economics and Energy 'Sonderforschungsbereich' TRR 267 (B05). Bavarian State Ministry of Health and Care German Research Foundation (DFG) The British Heart Foundation (BHF)/German Centre of Cardiovascular Research (DZHK) Collaboration German Federal Ministry of Education and Research (BMBF) Corona Foundation 'Deutsche Forschungsgemeinschaft (DFG)' 'Else-Kröner-Fresenius-Stiftung' (2020_EKSE.07), 'Else-Kröner-Forschungskolleg München', Technical University Munich, and the 'Deutsche Herzstiftung' (F/28/17) German Centre for Cardiovascular Research (DZHK; 81Z0600202) German Federal Ministry of Education and Research European Research Council (Starting grant 635872, CIRCODE) NHLBI NIH HHS RRM Charitable Fund European Research Council under the European Union's Horizon 2020 Research and Innovation Programme