Phagocytic NADPH Oxidase (NOX-2) as a Central Oxidative Effector in Experimental Models of Transportation-Noise-Induced Cardiovascular and Cerebral Disease

Transportation noise is an established cardiovascular risk factor. More than 112 million Europeans are chronically exposed above the thresholds of the Environmental Noise Directive, with approximately 73,000 premature deaths and 1.5 million disability-adjusted life years attributed annually. Large cohort studies demonstrate near-linear exposure–response relationships with ischaemic heart disease, myocardial infarction, stroke, heart failure and type 2 diabetes, and more recently with dementia, Alzheimer’s disease and Parkinson disease, independent of air pollution, detectable below guideline limits and stronger for night-time exposure. The noise reaction model attributes these effects to annoyance, sleep fragmentation and activation of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis, converging on oxidative stress, inflammation and endothelial dysfunction. This review argues that the phagocytic NADPH oxidase NOX-2 (gp91phox) is a decisive oxidative effector within that cascade in experimental models of noise exposure. NOX-2 is upregulated in the vasculature and brain after aircraft noise exposure, is delivered to the vessel wall largely by infiltrating myelomonocytic cells, and drives superoxide formation, peroxynitrite generation, and uncoupling of endothelial and neuronal nitric oxide synthase. Genetic deletion of Nox2 prevents, essentially, the entire vascular phenotype and attenuates cerebral oxidative stress and neuroinflammation, whereas ablation of lysozyme M-positive myeloid cells reproduces the vascular but not cerebral protection. These causal data derive predominantly from short-term rodent aircraft-noise models and require further extrapolation in chronic human exposure settings. In line with this proposed mechanism of action, noise-mediated organ damage can be mitigated by pharmacological and lifestyle-associated anti-oxidant interventions that are also briefly summarised here.