期刊
JOURNAL OF HEART AND LUNG TRANSPLANTATION
卷 41, 期 3, 页码 311-324出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.healun.2021.11.011
关键词
Basic; Translational; Clinical Research; Proteomics
资金
- Academy of Finland
- Jane and Aatos Erkko Foundation
- Sigrid Juselius Foundation
- Biomedicum Helsinki Foundation
- Helsinki University Hospital Research Funds
- Finnish Cultural Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Medical Association
- Finnish Transplantation Society
- Paavo Nurmi Foundation
- PaEuroivikki and Sakari Sohlberg Foundation
- University of Helsinki
The study investigated systemic changes in donor plasma proteome related to brain death and their impact on heart transplant outcomes. It found specific protein alterations in brain-dead donors compared to healthy controls, with implications for predicting transplant outcomes and improving donor evaluation. Analysis revealed upregulation of coagulation and glucose metabolism pathways in donors, and downregulation of complement activation and nitric oxide production pathways, among others. Notably, certain proteins were associated with post-transplant complications such as acute rejections and mortality, highlighting the potential clinical significance of these plasma proteome changes.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据