PDF(Pubmed)
Abstract：
Previous omics research in patients with complex congenital heart disease and single-ventricle circulation (irrespective of the stage of palliative repair) revealed alterations in cardiac and systemic metabolism, inter alia abnormalities in energy metabolism, and inflammation, oxidative stress or endothelial dysfunction. We employed an affinity-proteomics approach focused on cell surface markers, cytokines, and chemokines in the serum of 20 adult Fontan patients with a good functioning systemic left ventricle, and we 20 matched controls to reveal any specific processes on a cellular level. Analysis of 349 proteins revealed 4 altered protein levels related to chronic inflammation, with elevated levels of syndecan-1 and glycophorin-A, as well as decreased levels of leukemia inhibitory factor and nerve growth factor-ß in Fontan patients compared to controls. All in all, this means that Fontan circulation carries specific physiological and metabolic instabilities, including chronic inflammation, oxidative stress imbalance, and consequently, possible damage to cell structure and alterations in translational pathways. A combination of proteomics-based biomarkers and the traditional biomarkers (uric acid, γGT, and cholesterol) performed best in classification (patient vs. control). A metabolism- and signaling-based approach may be helpful for a better understanding of Fontan (patho-)physiology. Syndecan-1, glycophorin-A, leukemia inhibitory factor, and nerve growth factor-ß, especially in combination with uric acid, γGT, and cholesterol, might be interesting candidate parameters to complement traditional diagnostic imaging tools and the determination of traditional biomarkers, yielding a better understanding of the development of comorbidities in Fontan patients, and they may play a future role in the identification of targets to mitigate inflammation and comorbidities in Fontan patients.
摘要：
先前在患有复杂先天性心脏病和单心室循环的患者中进行的组学研究（与姑息性修复的阶段无关）揭示了心脏和全身代谢的改变。特别是能量代谢异常，和炎症，氧化应激或内皮功能障碍。我们采用了一种专注于细胞表面标记的亲和蛋白质组学方法，细胞因子,20名全身左心室功能良好的成年Fontan患者血清中的趋化因子，和我们20个匹配的对照，以揭示细胞水平上的任何特定过程。对349种蛋白质的分析显示，有4种与慢性炎症相关的蛋白质水平改变，随着syndecan-1和glyphorin-A水平的升高，以及与对照组相比，Fontan患者的白血病抑制因子和神经生长因子-β水平降低。总而言之，这意味着丰坦循环带有特定的生理和代谢不稳定性，包括慢性炎症,氧化应激失衡，因此，对细胞结构的可能损害和翻译途径的改变。基于蛋白质组学的生物标志物和传统生物标志物(尿酸，γGT,和胆固醇）在分类中表现最好（患者与控制)。基于代谢和信号传导的方法可能有助于更好地理解Fontan（病理）生理学。Syndecan-1,glyphorin-A,白血病抑制因子,和神经生长因子-β，尤其是与尿酸结合，γGT,和胆固醇，可能是有趣的候选参数，以补充传统的诊断成像工具和确定传统的生物标志物，更好地了解Fontan患者合并症的发展，它们可能在确定减轻Fontan患者炎症和合并症的靶标方面发挥未来作用。
