Abstract 49 Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting and pharmacological activation – molecular proof of a protective key role of endothelial α1AMPK

Clin Res Cardiol (2023). https://doi.org/10.1007/s00392-023-02180-w
Mitigation of aircraft noise-induced vascular dysfunction and oxidative stress by exercise, fasting and pharmacological activation – molecular proof of a protective key role of endothelial α1AMPK
P. Stamm¹, M. Kvandova¹, S. Rajilic², I. Schmal¹, D. Mihalikova¹, M. T. Bayo Jimenez¹, O. Hahad¹, M. Kollárová³, H. Ubbens¹, L. Strohm¹, M. Foretz⁴, B. Viollet⁴, Y. Ruan⁵, S. Jiang⁵, Q. Tang⁵, H. Kleinert⁶, S. Rapp¹, A. Gericke⁵, E. Schulz⁷, M. Oelze¹, J. F. Keaney⁸, A. Daiber¹, S. Kröller-Schön¹, T. Jansen¹, T. Münzel¹
¹Kardiologie 1, Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ²Klinik und Poliklinik für Herz-, Thorax- und Gefäßchirurgie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ³Institut of Physiology, Comenius University Bratislava, Bratislava, SK; ⁴INSERM U1016, Institut Cochin, Paris, FR; ⁵Augenklinik und Poliklinik, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ⁶Institut für Pharmakologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; ⁷Klinik für Kardiologie, Allgemeines Krankenhaus Celle, Celle; ⁸Division of Cardiovascular Medicine, UMass Medical School, Worcester, US;
Background: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually just in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or at least mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting and pharmacological treatment. Methods and Results: α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside (AICAR) application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure (maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)) produced significant endothelial dysfunction in the aorta and mesenteric arteries and retinal arterioles of wild-type mice (B6.Cg-Tg(Cdh5-cre)7Mlia/J). This was associated with increased vascular oxidative stress and asymmetric dimethylarginine (ADMA) formation. α1AMPK activation with all 3 approaches prevented endothelial dysfunction and vascular oxidative stress development, which was also supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. Conclusions: Our results clearly demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise and intermittent fasting effectively mitigate noise-induced cardiovascular damage. Future population-based studies have to clinically proof the concept of exercise/fasting-mediated mitigation of transportation noise associated disease. Support or Funding Information: Deutsche Forschungsgemeinschaft (S.K.-S. and T.J.), Boehringer Ingelheim Stiftung (A.D., T.J, T.M.) and Stiftung Mainzer Herz.
https://dgk.org/kongress_programme/jt2023/aP2212.html