AimsEpidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon.Methods and resultsWe developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II levels and induced endothelial dysfunction. Noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. Noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, nitrotyrosine-positive proteins and of endothelin-1. FACS analysis demonstrated an increase in infiltrated natural killer-cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4 days did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodelling, and cell death.ConclusionWe established a novel and unique aircraft noise stress model with increased blood pressure and vascular dysfunction associated with oxidative stress. This animal model enables future studies of molecular mechanisms, mitigation strategies, and pharmacological interventions to protect from noise-induced vascular damage.

AimsAircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice.Methods and resultsC57BL/6j and Nox2−/− (gp91phox−/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise of the mice caused the most pronounced vascular effects and dysregulation of Foxo3/circadian clock as revealed by next generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein down-regulation, and Nox2 activation. NGS revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, night-time aircraft noise increased oxidative stress, and inflammation biomarkers in serum.ConclusionAircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce night-time aircraft noise are warranted.

Cell viability studies of HT29 colon cancer cells treated with the CO-releasing compound [Mn(CO)(3)(tpm)]PF(6) revealed a significant photoinduced cytotoxicity comparable to that of established agent 5-fluorouracil (5-FU), while controls kept in the dark were unaffected at up to 100 microM.

Table of Contents Supplementary Methods General remarks Synthesis of RcPNA Cytotoxicity against mammalian cell lines Supplementary Figures and Tables Supplementary Table 1: Details on mass spectrometric identification of protein excised from preparative 2D gels. SupplementaryTable 2: Marker proteins induced after FcPNA and RcPNA treatment. Induction factors are displayed as averages over three independently performed biological experiments.

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