Short-term aircraft noise stress induces a fundamental metabolic shift in heart proteome and metabolome that bears the hallmarks of cardiovascular disease

Environmental stressors in the modern world can fundamentally affect human physiology and health. Exposure to stressors like air pollution, heat, and traffic noise has been linked to a pronounced increase in non-communicable diseases. Specifically, aircraft noise has been identified as a risk factor for cardiovascular and metabolic diseases, such as arteriosclerosis, heart failure, stroke, and diabetes. Noise stress leads to neuronal activation with subsequent stress hormone release that ultimately activates the renin-angiotensin-aldosterone system, increases inflammation and oxidative stress thus substantially affecting the cardiovascular system. However, despite the epidemiological evidence of a link between noise stress and metabolic dysfunction, the consequences of exposure at the molecular, metabolic level of the cardiovascular system are largely unknown. Here, we use a murine model system of short-term aircraft noise exposure to show that noise stress profoundly alters heart metabolism. Within 4 days of noise exposure, the heart proteome and metabolome bear the hallmarks of reduced potential for generating ATP from fatty-acid beta-oxidation, the tricarboxylic acid cycle, and the electron transport chain. This is accompanied by the increased expression of glycolytic metabolites, including the end-product, lactate, suggesting a compensatory shift of energy production towards anaerobic glycolysis. Intriguingly, the metabolic shift is reminiscent of what is observed in failing and ischaemic hearts. Mechanistically, we further show that the metabolic rewiring is likely driven by reactive oxygen species (ROS), as we can rescue the phenotype by knocking out NOX-2/gp91phox, a ROS inducer, in mice. Our results suggest that within a short exposure time, the cardiovascular system undergoes a fundamental metabolic shift that bears the hallmarks of cardiovascular disease. These findings underscore the urgent need to comprehend the molecular consequences of environmental stressors, paving the way for targeted interventions to mitigate health risks associated with chronic noise exposure in modern, environments heavily disturbed by noise pollution.