1Deutsches Herzzentrum München Erwachsenenkardiologie München, Deutschland; 2Deutsches Herzzentrum München Klinik für Herz- und Kreislauferkrankungen München, Deutschland
Exposure to psychosocial stress is a risk factor for many diseases, including atherosclerosis. Acute stress promotesvascular inflammation by increasing the uptake of pro-inflammatory leukocytes into atherosclerotic plaques fostering a pro-inflammatory, disease-propagating milieu. To improve cardiovascular health, it is crucial to develop stress-relief techniques, that can attenuate the inflammatory response. Here we show that prior physical activity modifies the acute response to stress. Mice with early atherosclerosis (ApoE-/- mice on a high cholesterol diet for 10 weeks) were either undisturbed (=sedentary) or had voluntary access to a running wheel for six weeks (=physical active) before being subjected to a single 3h mental stress episode. Immediately after cessation of mental stress, blood and aorta were harvested.
We found that physically active mice showed a lower reduction of blood leukocytes in response to stress. The fraction of blood leukocytes that was eliminated from the blood through stress was lower in active mice (71% vs 36%in sedentary vs active mice, respectively). We next performed cell tracking experiments using adoptive transferand confirmed that acute stress induced leukocyte re-distribution including a rapid uptake of blood leukocytes into atherosclerotic plaques, an effect that was abolished in active mice which showed stronger retention of inflammatory cells in the vasculature.
Next, we probed the consequence of these findings for vascular inflammation. Since active mice responded to stress with less re-distribution and more retention of leukocytes in the vasculature, we found less leukocytes inside plaques of active mice as revealed by flow cytometry and histology. Causally, prior physical activity lowered the stress-induced surge in local noradrenaline levels through a reduction in phosphorylation and hence activation of tyrosine hydroxylase - the rate-limiting enzyme in norepinephrine synthesis.
In conclusion, our data show that exercise beneficially modifies the adverse inflammatory response to acute mental stress.