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Alterations in the kallikrein-kinin system predict death after heart transplant
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 t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391369/ https://www.ncbi.nlm.nih.gov/pubmed/35986069 http://dx.doi.org/10.1038/s41598-022-18573-2 |
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author | 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. |
author_facet | 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. |
author_sort | Giangreco, Nicholas P. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9391369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93913692022-08-21 Alterations in the kallikrein-kinin system predict death after heart transplant 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. Sci Rep Article 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. Nature Publishing Group UK 2022-08-19 /pmc/articles/PMC9391369/ /pubmed/35986069 http://dx.doi.org/10.1038/s41598-022-18573-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article 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. Alterations in the kallikrein-kinin system predict death after heart transplant |
title | Alterations in the kallikrein-kinin system predict death after heart transplant |
title_full | Alterations in the kallikrein-kinin system predict death after heart transplant |
title_fullStr | Alterations in the kallikrein-kinin system predict death after heart transplant |
title_full_unstemmed | Alterations in the kallikrein-kinin system predict death after heart transplant |
title_short | Alterations in the kallikrein-kinin system predict death after heart transplant |
title_sort | alterations in the kallikrein-kinin system predict death after heart transplant |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391369/ https://www.ncbi.nlm.nih.gov/pubmed/35986069 http://dx.doi.org/10.1038/s41598-022-18573-2 |
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