Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death

J. Lukac, M. Saraswata, S. Joenvääräa, E. Holmström, K. Dhaygude, R. Krebs, A. Nykänen, R. Renkonen, K. Lemström

Research output: Contribution to journalConference articleScientificpeer-review

Abstract

Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-value
Original languageEnglish
JournalJournal of Heart and Lung Transplantation
Volume38
Issue number4, Supplement
Pages (from-to)S159
ISSN1053-2498
DOIs
Publication statusPublished - Apr 2019
MoE publication typeA4 Article in conference proceedings

Cite this

@article{760bf06ecc8446babe0aff81c9e86c93,
title = "Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death",
abstract = "Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-value",
author = "J. Lukac and M. Saraswata and S. Joenv{\"a}{\"a}r{\"a}a and E. Holmstr{\"o}m and K. Dhaygude and R. Krebs and A. Nyk{\"a}nen and R. Renkonen and K. Lemstr{\"o}m",
year = "2019",
month = "4",
doi = "10.1016/j.healun.2019.01.380",
language = "English",
volume = "38",
pages = "S159",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC",
number = "4, Supplement",

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Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death. / Lukac, J.; Saraswata, M.; Joenvääräa, S.; Holmström, E.; Dhaygude, K.; Krebs, R.; Nykänen, A.; Renkonen, R.; Lemström, K.

In: Journal of Heart and Lung Transplantation, Vol. 38, No. 4, Supplement, 04.2019, p. S159.

Research output: Contribution to journalConference articleScientificpeer-review

TY - JOUR

T1 - Label-Free Proteomics Approach Characterizes Plasma Protein Signature of Donor Brain Death

AU - Lukac, J.

AU - Saraswata, M.

AU - Joenvääräa, S.

AU - Holmström, E.

AU - Dhaygude, K.

AU - Krebs, R.

AU - Nykänen, A.

AU - Renkonen, R.

AU - Lemström, K.

PY - 2019/4

Y1 - 2019/4

N2 - Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-value

AB - Purpose Despite recent advances in donation after circulatory death, transplants from brain-dead donors remain the sole source in heart transplantation (HTx) worldwide. Due to organ shortage, marginal donors are increasingly used and the utilization of transplants becomes markedly more challenging. They undergo invariably brain death that induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of donor brain death on allografts is not well understood. Methods In a separate prospective, blinded single-center trial, we collected donor plasma samples and relevant clinical patient data from 50 HTx brain-dead donors and as controls plasma samples from age- and gender-matched 23 healthy volunteers. Quantitative label-free proteomics in high definition MSE mode (HDMSE) was carried out on the samples. Various statistical analyses were performed on quantitative proteomics data to obtain the most reliably distinguishing proteins, which classify the donors vs controls. Results With two or more unique proteins per identification, 463 proteins were quantified in our pilot study. A complete separation between donors and controls based on a set of 278 proteins (p-value

U2 - 10.1016/j.healun.2019.01.380

DO - 10.1016/j.healun.2019.01.380

M3 - Conference article

VL - 38

SP - S159

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

IS - 4, Supplement

ER -