Yin Xiaoke, Beele Alicia, Theofilatos Konstantinos, Baig Ferheen, Hasman Maria, Schmidt Lukas E, Boyle Joseph J, Turner Adam W, Miller Clint L, Pasterkamp Gerard, Stojkovic Stefan, Wojta Johann, Joner Michael, Mayr Manuel
National Heart and Lung Institute, Imperial College London, London, W12 0BZ, U.K.
Department of Cardiovascular Diseases, German Heart Centre Munich, TUM University Hospital, 80636 Munich, Germany.
J Proteome Res. 2025 Jul 4;24(7):3154-3159. doi: 10.1021/acs.jproteome.5c00152. Epub 2025 Jun 23.
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.
人体组织的蛋白质组学分析通常在尸检样本上进行。然而，尚未对尸检样本和新鲜冷冻样本的蛋白质组变化进行详细的比较分析。在本研究中，使用纳流液相色谱-串联质谱法（nanoflow LC-MS/MS）分析了来自已故患者的人体左前降支（LAD）冠状动脉样本（n = 94）。在一致性定量的蛋白质中，37%的蛋白质丰度与死后间隔时间（PMI）呈现显著相关性，其中大多数呈负相关。值得注意的是，随着PMI延长，平滑肌细胞标志物显著减少。相反，观察到免疫球蛋白、凝血因子和补体因子呈正相关，包括凝血因子XII、纤溶酶原和乳铁传递蛋白。对尸检LAD样本与新鲜冷冻LAD样本（n = 65）中性别特异性蛋白质变化的比较分析显示不一致。然而，在两组不同的新鲜冷冻颈动脉内膜切除术样本（n = 120和n = 200）之间观察到了强烈的相关性。本研究是首次对PMI对人体脉管系统蛋白质组成的影响进行大规模蛋白质组学研究，结果表明37%的定量蛋白质与PMI存在显著相关性。我们的研究结果强调了源自尸检样本的蛋白质组学数据在定量准确性方面可能存在的差异。因此，从尸检标本获得的结果在新鲜冷冻样本中可能无法重现。
