Alterations in the kallikrein-kinin system predict death after heart transplant.
Alterations in the kallikrein-kinin system predict death after heart transplant.
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DOI：
10.1038/s41598-022-18573-2
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发表时间：
2022-08-19
影响因子：
4.6
通讯作者：
Fine, Barry M.
中科院分区：
文献类型：
--
作者：
Giangreco, Nicholas P.;Lebreton, Guillaume;Restaino, Susan;Farr, Maryjane;Zorn, Emmanuel;Colombo, Paolo C.;Patel, Jignesh;Soni, Rajesh Kumar;Leprince, Pascal;Kobashigawa, Jon;Tatonetti, Nicholas P.;Fine, Barry M.
心脏移植仍然是终末期心力衰竭的决定性治疗方法。由于可用性有限，候选人的风险分层对于优化器官分配和移植结果至关重要。在这里，我们利用移植前的蛋白质组学来确定新的生物标志物，预测多机构队列中的移植后生存率。从血清样品中分离微囊泡，并使用质谱法进行蛋白质组学分析。蒙特卡罗交叉验证（MCCV）用于预测移植后的存活率，结合选择的受体移植前临床特征和血清微囊泡蛋白质组学数据。我们鉴定了预测性能高于AUROC 0.6的六种蛋白质标志物，包括凝血酶原（F2）、抗纤溶酶（SERPINF 2）、因子IX、羧肽酶2（CPB 2）、HGF激活剂（HGFAC）和低分子量激肽原（LK）。没有临床特征显示AUROC > 0.6。使用基因集富集分析（GSEA）评估推定的生物学功能和途径。差异表达分析鉴定了与移植后存活相关的移植前富集途径，包括移植前血小板活化和凝血途径。具体而言，移植前激肽释放酶-激肽系统（KKS）的凝血级联组分的上调和激肽原的下调与移植后的存活率相关。进一步的前瞻性研究是必要的，以确定是否在KKS的改变有助于移植后的总体生存。
Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort. Microvesicles were isolated from serum samples and underwent proteomic analysis using mass spectrometry. Monte Carlo cross-validation (MCCV) was used to predict survival after transplant incorporating select recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. We identified six protein markers with prediction performance above AUROC of 0.6, including Prothrombin (F2), anti-plasmin (SERPINF2), Factor IX, carboxypeptidase 2 (CPB2), HGF activator (HGFAC) and low molecular weight kininogen (LK). No clinical characteristics demonstrated an AUROC > 0.6. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA). Differential expression analysis identified enriched pathways prior to transplant that were associated with post-transplant survival including activation of platelets and the coagulation pathway prior to transplant. Specifically, upregulation of coagulation cascade components of the kallikrein-kinin system (KKS) and downregulation of kininogen prior to transplant were associated with survival after transplant. Further prospective studies are warranted to determine if alterations in the KKS contributes to overall post-transplant survival.
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影响因子：
7.4
作者：
Pichler P;Köcher T;Holzmann J;Mazanek M;Taus T;Ammerer G;Mechtler K
通讯作者：
Mechtler K
DOI：
10.1016/j.healun.2020.07.009
发表时间：
2020-10
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
Chambers DC;Zuckermann A;Cherikh WS;Harhay MO;Hayes D Jr;Hsich E;Khush KK;Potena L;Sadavarte A;Singh TP;Stehlik J;International Society for Heart and Lung Transplantation
通讯作者：
International Society for Heart and Lung Transplantation
影响因子：
7
作者：
Ross, PL;Huang, YLN;Pappin, DJ
通讯作者：
Pappin, DJ
影响因子：
20.3
作者：
Shariat-Madar, Zia;Mahdi, Fakhri;Schmaier, Alvin H.
通讯作者：
Schmaier, Alvin H.
影响因子：
8.9
作者：
Kobashigawa, Jon;Zuckermann, Andreas;Wagner, Florian
通讯作者：
Wagner, Florian