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通过组织学和组学分析鉴定人主动脉弓中的假定压力感受器

Identification of putative baroreceptors in human aortic arch by histological and omics analyses.

作者信息

Yundung Yankey, Pelisek Jaroslav, Maccio Umberto, Varga Zsuzsanna, Ech-Cherif Houria, Markkanen Enni, Rössler Fabian, Ouda Ahmed, Dzemali Omer, Zimmermann Alexander, Reutersberg Benedikt

机构信息

Department of Vascular Surgery, University Hospital Zurich, Zurich, Switzerland.

Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland.

出版信息

Hypertens Res. 2025 May 7. doi: 10.1038/s41440-025-02217-9.

Abstract

Baroreflex regulates blood pressure and heartbeat through specific mechanosensitive baroreceptors. However, the current knowledge is derived only from animal experiments. No data about human aortic baroreceptors have been reported so far. Therefore, in this study, we performed extended histological, proteomics and transcriptomics analyses of the aortic arch to identify potential human baroreceptors. Three healthy human aortic arches from autopsies, six abdominal aortic aneurysms and four control abdominal aortic tissue samples from our vascular biobank were analysed. For histological analyses, antibodies against various neuronal markers were used. Laser capture microdissection and macrodissection were performed to selectively analyse nerves in the adventitia of the human aorta using proteomics and RNA sequencing. Histological analysis revealed a heterogeneous distribution of nerves in the adventitia along the entire aortic arch, predominantly in the ascending aorta up to the left subclavian artery. Proteome analysis identified three putative human baroreceptors PIEZO1, TRPV2, and TRPM4. Transcriptomics confirmed that these ion channels do not originate from cells within the aortic wall but presumably from the cell body of the vagus nerve. Interestingly, these ion channels were also detected in the healthy abdominal aorta and abdominal aneurysm without any significant differences in their abundance. Our study identified, for the first time, putative baroreceptors in the human aortic arch. Further studies are necessary to validate our current results and elucidate the role of these putative baroreceptors in the human aortic arch.

摘要

压力感受器通过特定的机械敏感压力感受器调节血压和心跳。然而,目前的知识仅来自动物实验。迄今为止,尚未有关于人类主动脉压力感受器的数据报道。因此,在本研究中,我们对主动脉弓进行了扩展的组织学、蛋白质组学和转录组学分析,以识别潜在的人类压力感受器。分析了来自尸检的三个健康人类主动脉弓、六个腹主动脉瘤以及我们血管生物样本库中的四个对照腹主动脉组织样本。对于组织学分析,使用了针对各种神经元标记物的抗体。进行了激光捕获显微切割和宏观解剖,以使用蛋白质组学和RNA测序选择性地分析人类主动脉外膜中的神经。组织学分析显示,沿着整个主动脉弓,外膜中的神经分布不均,主要集中在升主动脉直至左锁骨下动脉。蛋白质组分析鉴定出三种假定的人类压力感受器PIEZO1、TRPV2和TRPM4。转录组学证实,这些离子通道并非起源于主动脉壁内的细胞,而是可能起源于迷走神经的细胞体。有趣的是,在健康的腹主动脉和腹主动脉瘤中也检测到了这些离子通道,其丰度没有任何显著差异。我们的研究首次在人类主动脉弓中鉴定出假定的压力感受器。需要进一步的研究来验证我们目前的结果,并阐明这些假定的压力感受器在人类主动脉弓中的作用。

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