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Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects
Basic Research in Cardiology ( IF 9.5 ) Pub Date : 2021-04-30 , DOI: 10.1007/s00395-021-00869-5
Katie Frenis 1 , Johanna Helmstädter 1 , Yue Ruan 2 , Eva Schramm 3 , Sanela Kalinovic 1 , Swenja Kröller-Schön 1 , Maria Teresa Bayo Jimenez 1 , Omar Hahad 1, 4 , Matthias Oelze 1 , Subao Jiang 2 , Philip Wenzel 1, 4, 5 , Clemens J Sommer 6 , Katrin B M Frauenknecht 6 , Ari Waisman 3 , Adrian Gericke 2 , Andreas Daiber 1, 4 , Thomas Münzel 1, 4 , Sebastian Steven 1, 5
Affiliation  

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6GLy6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.



中文翻译:

溶菌酶 M 阳性细胞的消融可防止飞机噪音引起的血管损伤而不改善脑副作用

飞机噪音会引起血管和脑部炎症和氧化应激,从而导致高血压和心血管/脑功能障碍。通过目前的研究,我们试图确定骨髓细胞在暴露于飞机噪音的血管与大脑后果中的作用。在携带 cre 诱导型白喉毒素受体的 LysMCre iDTR小鼠中进行了毒素介导的溶菌酶 M + (LysM + ) 骨髓细胞消融。在毒素处理的最后 4 天,动物暴露在最大和平均声压级分别为 85 和 72 dB(A) 的噪音中。流式细胞仪分析显示 CD45 +、CD11b +、F4/80 +和 Ly6G -的积累LysM +阻止了噪声暴露小鼠主动脉中的Ly6C +细胞外周细胞消融,而脑浸润甚至在消融时加剧。飞机噪声引起的血压升高和主动脉和视网膜/肠系膜小动脉的内皮功能障碍几乎完全通过消融恢复正常。相应地,在消融噪声暴露的小鼠中,主动脉、心脏和视网膜/肠系膜血管中的活性氧减少,而大脑中的小胶质细胞活化和丰度大大增加。吞噬性 NADPH 氧化酶 (NOX-2) 和血管细胞粘附分子-1 (VCAM-1) mRNA 在主动脉中的表达降低,而消融后大脑中的 NFκB 信号似乎被激活。总之,我们展示了 LysM +后对飞机噪音的反应脑和外周炎症反应的解离细胞消融,其中外周髓性炎症细胞代表噪声应激诱导的心血管效应的病理机制的主要部分,它们的中枢神经对应物小胶质细胞是应激反应的关键介质。

更新日期:2021-04-30
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