Universität zu Köln

Lukac, Jan ORCID: 0000-0002-9492-8218, Dhaygude, Kishor ORCID: 0000-0003-4499-6180, Saraswat, Mayank ORCID: 0000-0002-5021-8150, Joenvaara, Sakari, Syrjala, Simo O., Holmstrom, Emil J., Krebs, Rainer ORCID: 0000-0003-0418-8226, Renkonen, Risto, Nykanen, Antti, I and Lemstrom, Karl B. (2022). Plasma proteome of brain-dead organ donors predicts heart transplant outcome. J. Heart Lung Transplant., 41 (3). S. 311 - 325. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1557-3117

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lukac, Jan UNSPECIFIED orcid.org/0000-0002-9492-8218 UNSPECIFIED Dhaygude, Kishor UNSPECIFIED orcid.org/0000-0003-4499-6180 UNSPECIFIED Saraswat, Mayank UNSPECIFIED orcid.org/0000-0002-5021-8150 UNSPECIFIED Joenvaara, Sakari UNSPECIFIED UNSPECIFIED UNSPECIFIED Syrjala, Simo O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holmstrom, Emil J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Krebs, Rainer UNSPECIFIED orcid.org/0000-0003-0418-8226 UNSPECIFIED Renkonen, Risto UNSPECIFIED UNSPECIFIED UNSPECIFIED Nykanen, Antti, I UNSPECIFIED UNSPECIFIED UNSPECIFIED Lemstrom, Karl B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-680026
DOI:	10.1016/j.healun.2021.11.011
Journal or Publication Title:	J. Heart Lung Transplant.
Volume:	41
Number:	3
Page Range:	S. 311 - 325
Date:	2022
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1557-3117
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language COAGULATION; INJURY; PERFORMANCE; COMPLEMENT; PATHWAYS; LONG Multiple languages Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68002