A Comparative Proteomics Study of Autopsy and Fresh-Frozen Coronary Artery Samples.

IF 3.6 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Proteome Research Pub Date : 2025-07-04 Epub Date: 2025-06-23 DOI:10.1021/acs.jproteome.5c00152

Xiaoke Yin, Alicia Beele, Konstantinos Theofilatos, Ferheen Baig, Maria Hasman, Lukas E Schmidt, Joseph J Boyle, Adam W Turner, Clint L Miller, Gerard Pasterkamp, Stefan Stojkovic, Johann Wojta, Michael Joner, Manuel Mayr

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Abstract

Proteomic analyses of human tissues are often conducted on autopsy samples. However, no detailed comparative analysis between proteomic changes derived from autopsy samples and fresh-frozen samples has been undertaken. In this study, human left anterior descending (LAD) coronary artery samples (n = 94) from deceased patients were analyzed using nanoflow LC-MS/MS. Among consistently quantified proteins, 37% of the protein abundances exhibited significant correlations with the post-mortem interval (PMI), most of which are inverse. Notably, smooth muscle cell markers displayed substantial reduction with prolonged PMI. Conversely, positive correlations were observed for immunoglobulins, coagulation factors, and complement factors, including coagulation factor XII, plasminogen, and lactotransferrin. Comparative analyses of sex-specific protein changes in autopsy LAD samples versus fresh-frozen LAD samples (n = 65) showed no concordance. However, a robust correlation was observed between 2 different cohorts of fresh-frozen carotid endarterectomies (n = 120 and n = 200). This study represents the first large-scale proteomics investigation into the influence of PMI on the protein composition of the human vasculature, showing significant correlations with PMI for 37% of the quantified proteins. Our findings underscore potential discrepancies in the quantitative accuracy of proteomics data derived from autopsy samples. Consequently, results obtained from post-mortem specimens may not be reproducible in fresh-frozen samples.

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解剖和新鲜冷冻冠状动脉样本的蛋白质组学比较研究。

人体组织的蛋白质组学分析经常在尸检样本上进行。然而，尚未对尸体解剖样本和新鲜冷冻样本的蛋白质组学变化进行详细的比较分析。在这项研究中，使用纳米流LC-MS/MS分析了来自死者的人类左前降支（LAD）冠状动脉样本（n = 94）。在一致量化的蛋白质中，37%的蛋白质丰度与死后间隔（PMI）呈显著相关，其中大部分呈负相关。值得注意的是，随着PMI的延长，平滑肌细胞标记物显示出明显的减少。相反，免疫球蛋白、凝血因子和补体因子（包括凝血因子XII、纤溶酶原和乳转铁蛋白）呈正相关。尸检LAD样本与新鲜冷冻LAD样本（n = 65）的性别特异性蛋白变化对比分析显示没有一致性。然而，在两个不同的新鲜冷冻颈动脉内膜切除术队列（n = 120和n = 200）之间观察到强相关性。该研究首次对PMI对人体脉管系统蛋白质组成的影响进行了大规模的蛋白质组学研究，结果显示37%的定量蛋白与PMI存在显著相关性。我们的发现强调了来自尸检样本的蛋白质组学数据的定量准确性的潜在差异。因此，从死后标本中获得的结果可能无法在新鲜冷冻样品中重现。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Proteome Research 生物-生化研究方法

CiteScore

9.00

自引率

4.50%

发文量

251

审稿时长

3 months

期刊介绍： Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".