α1AMPK as a target of preventive strategies against aircraft noise induced (vascular) stress:aircraft noise induced cardiovascular complications – pharmacological (metformin) and non-pharmacological (physical exercise and fasting) α1AMPK mediated interven

噪声作为一种环境危险因素及其对人类的影响越来越成为科学界关注的焦点。根据几项流行病学研究，世界卫生组织估计，暴露在环境噪音中会损失100万健康生命年。我们的研究小组可以证明，健康成年人暴露在夜间噪音中不仅会导致睡眠节律中断，还会导致血压、脉搏和应激激素水平升高。尽管有很多分析集中在噪音对农场动物的行为模式、生育能力和产奶量等方面的影响上，但几乎没有动物模型系统来研究噪音对血管的影响。我们只能找到三篇使用高声压级（≥100 dBA）噪声暴露协议的动物噪声暴露对心血管功能影响的出版物。这很可能会导致动物耳蜗的听觉损伤。基于这些先前的研究，我们的团队开发了一个噪音暴露模型，具有较低的峰值声级（<85 dBA），较低的平均声压级（72 dBA）。AMP依赖性蛋白激酶（AMPK）是一种普遍表达的酶，它作为能量传感器，因为AMP和ATP之间的比例决定了它的活性。在心血管系统中，已知AMPK激活NO生成酶eNOS并促进血管生成。我们的研究小组可以证明血管异构体能够抑制血管氧化应激的来源，以维持内皮功能。AMPK与AICAR的药理激活可改善血管紧张素II诱导的血管功能障碍和氧化应激。此外，AMPK在运动训练对血管系统的保护作用中起重要作用。虽然运动训练对心血管风险的有益影响是众所周知的，但社会趋势是减少体育锻炼。另一种替代体力消耗的方法是间歇性禁食或热量限制，流行病学研究支持这与减少心血管事件的明显相关性。这里提到的生活方式（运动训练，禁食或热量限制）显示出对心血管系统的有益影响，这主要依赖于AMPK。因此，目前的主要目的是研究这些策略是否可以用来减少噪声引起的血管应激。

Noise as an environmental risk factor and its effects on humans are coming more and more into the focus of scientific interest. The WHO estimates a loss of one million healthy life years due to environmental noise exposure supported by several epidemiological studies. Our group could show that nighttime noise exposure of healthy adults not only lead to a disruption of sleep rhythm but also increased blood pressure, pulse and levels of stress hormones There are almost no animal model systems to study the vascular consequences of noise although there are a lot of analyses focusing on the effects of noise on the behavior pattern, fertility and production of milk etc. in farm animals. We could only find three publications on the effects of noise exposure of animals on cardiovascular function using noise exposure protocols high sound pressure levels (≥100 dBA). Most likely this will lead to an auditory damage of the animals’ cochlea. Based on these previous studies our group developed a noise exposure model with lower peak sound levels (<85 dBA), lower mean sound pressure levels (72 dBA).The AMP-dependent protein kinase (AMPK) is a ubiquitously expressed enzyme which acts as an energy sensor since the ratio between AMP and ATP determines its activity. In the cardiovascular system AMPK in known to activate the NO generating enzyme eNOS and is promoting angiogenesis. Our group could show that the vascular isoform is able to inhibit sources of vascular oxidative stress to maintain endothelial function. The pharmacological activation of AMPK with AICAR lead to an improvement of angiotensin II induced vascular dysfunction and oxidative stress. Furthermore AMPK plays an important role mediating protective effects of exercise training on the vascular system. Although the beneficial effects of exercise training on the cardiovascular risk are known there is a social trend towards less physical activity. An alternative to physical exertion would be intermittent fasting or caloric restriction, which shows a clear correlation with less cardiovascular events supported by epidemiological studies. The here mentioned lifestyle (exercise training, fasting or caloric restriction) show beneficial effects on the cardiovascular system which are mostly AMPK dependent. Therefore, the major aims of the current proposal are to study if these strategies can be used to reduce noise-induced vascular stress.