Ulrike Meyer-Lindemann, Karina Borbil, Marius Schwab, Aldo Moggio, Rui Shen, M. Amin Sharifi, Tan An Dang, Viktoria Schories, Raphael Rottenkolber, Svenja Rapelius, Julia Hinterdobler, Carina Mauersberger, Moritz von Scheidt, Lars Mäegdefessel, Henning Wackerhage, Karsten Köhler, Egija Berga-Švītiņa, Baiba Vilne, Michael Hristov, Christian Weber, Sabine Steffens, Cameron S. McAlpine, Heribert Schunkert, Thorsten Kessler, Hendrik B. Sager
Mental stress is a major risk factor for cardiovascular disease, yet no targeted therapies exist to reduce stress-related vascular risk. We investigated whether physical activity mitigates the adverse cardiovascular effects of acute mental stress and explored the underlying mechanisms. Sedentary and physically active mice, following 6 weeks of voluntary treadmill running, were exposed to acute mental stress, and inflammatory responses within atherosclerotic plaques were assessed. Physically active mice exhibited markedly reduced stress-induced leukocyte infiltration into plaques compared with sedentary mice. This protective effect was associated with blunted stress-induced norepinephrine release and reduced endothelial activation, reflected by lower expression of adhesion molecules and chemokines. To assess translational relevance, physically active and inactive human participants were exposed to acute stress, revealing that physical activity similarly attenuated stress-induced leukocyte redistribution. These findings demonstrate that physical activity counteracts stress-induced vascular inflammation and highlight its potential as a preventive and therapeutic strategy to reduce stress-related cardiovascular risk.