Environmental stressors such as noise have been associated with cardiovascular diseases. However, the underlying mechanisms are unknown. A new experimental model of aircraft noise stress developed by Münzel and colleagues might help to elucidate these molecular mechanisms, as well as enable testing of possible therapeutic interventions. With the use of this experimental mouse model, the investigators demonstrated that aircraft noise induces endothelial dysfunction and increases inflammation and oxidative stress in the vasculature.
The aircraft noise model consisted of repetitive playbacks of 2 h noise patterns of 69 aircraft noise events of 43 s (maximum sound level of 85 dBA and mean sound level of 72 dBA) applied by loudspeakers, separated by periods of silence at irregular intervals, for 4 days. These noise levels are considered to be safe, and are much lower than levels used in previous studies.
Münzel et al. found that mice exposed to noise had endothelial dysfunction, with increased endothelial nitric oxide synthase uncoupling, and had elevated systolic blood pressure and high plasma levels of stress hormones and angiotensin II. Noise also increased nitrosative and oxidative stress, with activation of NADPH oxidase and elevated levels of endothelin 1 and 3-nitrotyrosine in vascular tissue. Flow cytometry analysis showed infiltration of natural killer cells and neutrophils into the vasculature. Mice exposed to similar levels of white noise did not show any of these changes. Next-generation sequencing analysis to identify potential noise stress-response genes showed that exposure to aircraft noise altered the expression of genes associated with vascular function, cell death, and forkhead box O signalling pathways associated with stress adaptation.
“The demonstration of an involvement of NADPH oxidase and an uncoupled nitric oxide synthase in causing vascular damage in response to noise stress suggests that in people who already have cardiovascular risk factors, the development of atherosclerosis is accelerated with exposure to noise,” explains Münzel. “Environmental stressors such as noise and air pollution have to be accepted as novel cardiovascular risk factors,” he remarks. However, Münzel points out that so far only the ESC cardiovascular prevention guidelines mention air pollution, with no mention to noise stressors.
Münzel and colleagues are now testing the influence of cardiovascular drugs, such as angiotensin-receptor blockers or statins, in noise-induced vascular dysfunction, and will assess the effects of noise in different mouse models of cardiovascular disease. The investigators are also testing the effects of noise on vascular function in healthy individuals and in patients with coronary artery disease, combining tools for vascular function measurement with tools from sleep research. “To my knowledge, our approach to noise research is unique,” says Münzel. “I hope that many groups use our model and in the near future we can make huge progress in noise research that will help people exposed to transportation noise.”
Münzel, T. et al. Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice. Eur. Heart J. http://dx.doi.org/10.1093/eurheartj/ehx081 (2017)
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Fernández-Ruiz, I. Aircraft noise impairs vascular function. Nat Rev Cardiol 14, 191 (2017). https://doi.org/10.1038/nrcardio.2017.32