Plasma proteome of brain-dead organ donors predicts heart transplant outcome

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Lukac , J , Dhaygude , K , Saraswat , M , Joenväärä , S , Syrjälä , S O , Holmström , E J , Krebs , R , Renkonen , R , Nykänen , A I & Lemström , K B 2022 , ' Plasma proteome of brain-dead organ donors predicts heart transplant outcome ' , Journal of Heart and Lung Transplantation , vol. 41 , no. 3 , pp. 311-324 .

Title: Plasma proteome of brain-dead organ donors predicts heart transplant outcome
Author: Lukac, Jan; Dhaygude, Kishor; Saraswat, Mayank; Joenväärä, Sakari; Syrjälä, Simo O.; Holmström, Emil J.; Krebs, Rainer; Renkonen, Risto; Nykänen, Antti I.; Lemström, Karl B.
Contributor organization: Department of Pathology
University of Helsinki
TRIMM - Translational Immunology Research Program
Department of Biochemistry and Developmental Biology
HUS Heart and Lung Center
Helsinki University Hospital Area
III kirurgian klinikka
Transplantation Laboratory
Department of Bacteriology and Immunology
Infection Biology Research Program
Risto Renkonen / Principal Investigator
Department of Surgery
Date: 2022-03-01
Language: eng
Number of pages: 14
Belongs to series: Journal of Heart and Lung Transplantation
ISSN: 1053-2498
Abstract: Background: The pathophysiological changes related to brain death may affect the quality of the transplanted organs and expose the recipients to risks. We probed systemic changes reflected in donor plasma proteome and investigated their relationship to heart transplant outcomes. Methods: Plasma samples from brain-dead multi-organ donors were analyzed by label-free protein quantification using high-definition mass spectrometry. Unsupervised and supervised statistical models were used to determine proteome differences between brain-dead donors and healthy controls. Proteome variation and the corresponding biological pathways were analyzed and correlated with transplant outcomes. Results: Statistical models revealed that donors had a unique but heterogeneous plasma proteome with 237 of 463 proteins being changed compared to controls. Pathway analysis showed that coagulation, gluconeogenesis, and glycolysis pathways were upregulated in donors, while complement, LXR/RXR activation, and production of nitric oxide and reactive oxygen species in macrophages pathways were downregulated. In point-biserial correlation analysis, lysine-specific demethylase 3A was moderately correlated with any grade and severe PGD. In univariate and multivariate Cox regression analyses myosin Va and proteasome activator complex subunit 2 were significantly associated with the development of acute rejections with hemodynamic compromise within 30 days. Finally, we found that elevated levels of lysine-specific demethylase 3A and moesin were identified as predictors for graft-related 1-year mortality in univariate analysis. Conclusions: We show that brain death significantly changed plasma proteome signature Donor plasma protein changes related to endothelial cell and cardiomyocyte function, inflammation, and vascular growth and arteriogenesis could predict transplant outcome suggesting a role in donor evaluation.
Description: Publisher Copyright: © 2021 The Authors
Subject: Basic
Clinical Research
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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