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主动脉瓣狭窄患者心房和心室心脏组织的蛋白质组学图谱。

Proteomic mapping of atrial and ventricular heart tissue in patients with aortic valve stenosis.

机构信息

Department for Pediatric Cardiology, Intensive Care and Pulmonology, University Medical Center, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

DZHK (German Center for Cardiovascular Research), Partner Site of Göttingen, Göttingen, Germany.

出版信息

Sci Rep. 2021 Dec 22;11(1):24389. doi: 10.1038/s41598-021-03907-3.

DOI:10.1038/s41598-021-03907-3
PMID:34937869
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8695579/
Abstract

Aortic valve stenosis (AVS) is one of the most common valve diseases in the world. However, detailed biological understanding of the myocardial changes in AVS hearts on the proteome level is still lacking. Proteomic studies using high-resolution mass spectrometry of formalin-fixed and paraffin-embedded (FFPE) human myocardial tissue of AVS-patients are very rare due to methodical issues. To overcome these issues this study used high resolution mass spectrometry in combination with a stem cell-derived cardiac specific protein quantification-standard to profile the proteomes of 17 atrial and 29 left ventricular myocardial FFPE human myocardial tissue samples from AVS-patients. In our proteomic analysis we quantified a median of 1980 (range 1495-2281) proteins in every single sample and identified significant upregulation of 239 proteins in atrial and 54 proteins in ventricular myocardium. We compared the proteins with published data. Well studied proteins reflect disease-related changes in AVS, such as cardiac hypertrophy, development of fibrosis, impairment of mitochondria and downregulated blood supply. In summary, we provide both a workflow for quantitative proteomics of human FFPE heart tissue and a comprehensive proteomic resource for AVS induced changes in the human myocardium.

摘要

主动脉瓣狭窄（AVS）是世界上最常见的瓣膜疾病之一。然而，对于 AVS 心脏在蛋白质组水平上的心肌变化的详细生物学理解仍然缺乏。由于方法学问题，使用福尔马林固定和石蜡包埋（FFPE）的人类 AVS 患者心肌组织的高分辨率质谱进行蛋白质组学研究非常罕见。为了克服这些问题，本研究使用高分辨率质谱结合干细胞衍生的心脏特异性蛋白质定量标准，对 17 例心房和 29 例左心室 FFPE 人类 AVS 患者心肌组织样本的蛋白质组进行了分析。在我们的蛋白质组学分析中，我们在每个样本中定量了中位数为 1980 个（范围为 1495-2281 个）蛋白质，并鉴定出心房中有 239 个蛋白质和心室中有 54 个蛋白质显著上调。我们将这些蛋白质与已发表的数据进行了比较。研究充分的蛋白质反映了 AVS 相关的疾病变化，如心脏肥大、纤维化的发展、线粒体功能障碍和血液供应减少。总之，我们提供了一种用于人类 FFPE 心脏组织定量蛋白质组学的工作流程，并提供了一个全面的蛋白质组资源，用于研究 AVS 引起的人类心肌变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/3b0a0db92575/41598_2021_3907_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/0f090abdf646/41598_2021_3907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/1d099da72967/41598_2021_3907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/ffd7301db656/41598_2021_3907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/f3b591d31fa5/41598_2021_3907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/3b0a0db92575/41598_2021_3907_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/0f090abdf646/41598_2021_3907_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/1d099da72967/41598_2021_3907_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/ffd7301db656/41598_2021_3907_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/f3b591d31fa5/41598_2021_3907_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdb8/8695579/3b0a0db92575/41598_2021_3907_Fig5_HTML.jpg

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