Noise‐induced vascular dysfunction, oxidative stress and inflammationare improved by pharmacological heme oxygenase‐1 induction

Abstract

Endothelial dysfunction, vascular oxidative stress and inflammation are consequences of traditional cardiovascular risk factors and triggers of cardiovascular disease. However, emerging environmental stressors such as traffic noise exposure may facilitate the development of cardiovascular and metabolic diseases.C57BL/6J mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) applied for 1, 2 and 4 days caused an increase in systolic blood pressure, stress hormones and induced endothelial dysfunction, oxidative stress and inflammation (Eur Heart J 2017). We also observed reduced vascular NO levels due to eNOS uncoupling and increased levels of nitrotyrosine, interleukin‐6, NADPH oxidase isoform Nox2 and endothelin‐1 in the mice exposed to aircraft noise. More recently, we have shown that aircraft noise induces also cerebral oxidative stress and a neuroinflammatory phenotype that is up‐stream of the observed adverse cardiovascular effects, all of which was normalized by genetic deletion of NADPH oxidase isoform Nox2 (Eur Heart J 2018).The role of heme oxygenase‐1 (HO‐1) as an antioxidant response is currently being investigated. C57BL/6J mice were treated with the HO‐1 activator hemin (25 mg/kg i.p.). Our preliminary data show a protective effect of hemin infusion on aircraft noise exposure (4 days) induced increase of systolic blood pressure and vascular dysfunction. There was also a trend of normalization of noise‐triggered oxidative stress ny hemin infusion. Within the ongoing studies, we will address the impact of HO‐1 induction in noise‐exposed mice on expression of genes and proteins involved in pathways of oxidative stress and systemic inflammation. In a later stage of the study, we will also test whether genetic deficiency of HO‐1 (HO‐1+/− mice) aggravates and the Nrf2 activator dimethyl fumarate (DMF) ameliorates noise‐triggered cardiovascular complications. The present study aims at identifying new targets for mitigation strategies against adverse health effects of environmental noise exposure of the general population. Since HO‐1 and Nrf2 induction can be achieved by natural dietary constituents, these pathways represent promising targets for preventive measures.Support or Funding InformationOur experimental studies on noise effects in mice were supported by vascular biology research grants from the Else‐Kröner‐Fresenius Foundation for “Noise and arterial hypertension” (2017_A106) and the Boehringer Ingelheim Foundation for the collaborative research group „Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications”.