Bosi Dong, Xin Li, Lu Zhang, Ge Liang, Wen Zheng, Luolan Gui, Shuming Ji, Yusha Tang, Hua Li, Wanling Li, Ruiqi Yang, Yajiao Li, Anjiao Peng, Yucheng Chen, Meng Gong, Lei Chen
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引用次数: 0
Abstract
Patent foramen ovale (PFO), a cardiac anatomical anomaly inducing abnormal haemodynamics, leads to a paradoxical bypass of the pulmonary circulation. PFO closure might alleviate migraines; however, clinical evidence and basic experiments for the relationship are lacking. To explore the effect of PFO on migraine, 371 migraineurs finishing blood tests and contrast transthoracic echocardiography for the detection of PFO were prospectively included. Multivariate regression analysis revealed that PFO was independently associated with aura, and lower cystatin-C (cys-C) and calcium levels. Among them, patients with PFO who underwent percutaneous PFO closure were continuously followed up 1 year after the operation. The intensity of migraine was significantly relieved and the levels of cys-C and calcium increased after PFO closure. Untargeted and targeted metabolomics of plasma from migraineurs before and after PFO closure revealed that 5-HT and glutathione (GSH) metabolites were differentially expressed after PFO closure. The differential metabolites were then validated in the plasma and brain tissues of PFO mouse models by LC-MS/MS analysis. Desorption electrospray ionization mass imaging demonstrated that these metabolic alterations occurred mainly in the posterior cerebral cortex. Collectively, aura, cys-C and calcium could be biomarkers of migraineurs with PFO. PFO might have an impact on the posterior head associated with the regulation of 5-HT and GSH. PFO closure might relieve migraine by improving 5-HT clearance metabolism and ameliorating redox reactions. Our results may provide evidence for an indication of PFO closure in migraine and support the related potential mechanism. KEY POINTS: Aura, and levels of cystatin-C and calcium are biomarkers of migraineurs with a patent foramen ovale (PFO). The clearance of pulmonary metabolism of 5-HT and deoxygenated blood might be the reason for the improvement of migraine symptoms in patients with PFO. The posterior region of the brain is the main area responsible for PFO-induced migraine.
卵圆孔未闭（PFO）是一种心脏解剖异常，引起异常血流动力学，导致肺循环的矛盾旁路。PFO闭合可能缓解偏头痛；然而，缺乏相关的临床证据和基础实验。为了探讨PFO对偏头痛的影响，我们前瞻性地纳入了371例偏头痛患者的血液检查和经胸超声心动图造影剂检测PFO。多因素回归分析显示，PFO与先气、较低的胱他汀- c （cys-C）和钙水平独立相关。其中经皮闭合PFO患者术后持续随访1年。PFO关闭后，偏头痛强度明显减轻，cys-C和钙水平升高。PFO关闭前后偏头痛患者血浆的非靶向和靶向代谢组学显示，PFO关闭后5-HT和谷胱甘肽（GSH）代谢物表达存在差异。然后通过LC-MS/MS分析验证PFO小鼠模型血浆和脑组织中的差异代谢物。解吸电喷雾质量成像显示这些代谢改变主要发生在大脑后皮层。总的来说，先兆、cys-C和钙可能是偏头痛伴PFO的生物标志物。PFO可能与5-羟色胺和谷胱甘肽的调节有关，对后脑有影响。PFO关闭可能通过改善5-HT清除代谢和改善氧化还原反应来缓解偏头痛。我们的结果可能为偏头痛的PFO关闭指征提供证据，并支持相关的潜在机制。重点：先兆、胱抑素c和钙水平是伴有卵圆孔未闭（PFO）偏头痛的生物标志物。肺代谢5-羟色胺和脱氧血的清除可能是PFO患者偏头痛症状改善的原因。大脑后部区域是pfo诱发偏头痛的主要区域。
期刊介绍：
The Journal of Physiology publishes full-length original Research Papers and Techniques for Physiology, which are short papers aimed at disseminating new techniques for physiological research. Articles solicited by the Editorial Board include Perspectives, Symposium Reports and Topical Reviews, which highlight areas of special physiological interest. CrossTalk articles are short editorial-style invited articles framing a debate between experts in the field on controversial topics. Letters to the Editor and Journal Club articles are also published. All categories of papers are subjected to peer reivew.
The Journal of Physiology welcomes submitted research papers in all areas of physiology. Authors should present original work that illustrates new physiological principles or mechanisms. Papers on work at the molecular level, at the level of the cell membrane, single cells, tissues or organs and on systems physiology are all acceptable. Theoretical papers and papers that use computational models to further our understanding of physiological processes will be considered if based on experimentally derived data and if the hypothesis advanced is directly amenable to experimental testing. While emphasis is on human and mammalian physiology, work on lower vertebrate or invertebrate preparations may be suitable if it furthers the understanding of the functioning of other organisms including mammals.
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