Background:
Previous studies demonstrated that environmental risk factors such as traffic (aircraft) noise exposure increase cardiovascular oxidative stress by NADPH oxidase activation and endothelial nitric oxide synthase uncoupling resulting in endothelial dysfunction and vascular inflammation. The beneficial (antioxidant and anti-inflammatory) effect of α1AMPK activation was highlighted in different animal models of oxidative stress conditions. Therefore, in the present study, we investigated the protective role of α1AMPK activation during intermittent fasting (physiological activation) against aircraft noise exposure mediated cardiovascular complications.
Methods and Results:
To determine the role of tissue-specific α1AMPK, endothelial α1AMPK knockout (AMPKfl/fl x CdhCre+) and corresponding wild type (CdhCre+) mice were exposed to aircraft noise (maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)) for the last 4 days after seven weeks of intermittent fasting. Physiological activation of α1AMPK was induced by intermittent fasting (2 weeks - normal food intake; 2 weeks -10 % reduction and 3 weeks – 35 % reduction of calorie restriction). We could show that 4 days of noise exposure lead to significant endothelial dysfunction in the aorta and a. mesenterica, which was associated with increased oxidative stress and endothelial nitric oxide synthase uncoupling. Intermittent fasting resulted in a marked improvement of endothelium-dependent relaxation mediated by preserved eNOS signaling and increased NO production. This was accompanied by oxidative stress reduction reflected by decreased expression of NADPH oxidase 2 (NOX-2) in wild-type mice. In contrast, intermittent fasting had no protective effect on noise-induced damage in endothelial-specific α1AMPK knockout animals. Moreover, we observed a reduction of cerebral oxidative stress due to decreased expression of NADPH oxidases (NOX‐1, NOX‐2), which was also endothelial α1AMPK dependent.
Conclusion:
Here we present novel data on intermittent fasting–mediated activation of α1AMPK as a protective strategy against the cardiovascular complications mediated by aircraft noise exposure. Selective endothelial α1AMPK activation could represent a suitable future tool to lower noise-induced vascular damage. Especially patients at high cardiovascular risk, with pre-existing cardio-metabolic disease or elderly patients, could benefit from supervised intermittent fasting to prevent additive cardio/cerebrovascular damage in response to transportation noise exposure.
Support or Funding Information: German Research Foundation (Deutsche Forschungsgemeinschaft) DFG