Rejection-associated Mitochondrial Impairment After Heart Transplantation

Overview

Journal Transplant Direct

Publisher Wolters Kluwer

Specialty General Surgery

Date 2020 Nov 2

PMID 33134492

Citations 6

Authors

Erick Romero

Eleanor Chang

Esteban Tabak

Diego Pinheiro

Jose Tallaj

Silvio Litovsky

Brendan Keating

Mario Deng

Martin Cadeiras

Affiliations

Soon will be listed here.

Abstract

Background: Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs.

Methods: We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters.

Results: The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejection samples, rejection samples had a decreased activity of mitochondrial-related genes and an increased activity of immune-response genes. Biologic processes and hub genes in the mitochondria-related modules were primarily involved with energy generation, substrate metabolism, and regulation of oxidative stress. Compared with International Society of Heart and Lung Transplantation criteria, GE-based classification had stronger correlation to the weighted gene coexpression network analysis-derived functional modules. The brain natriuretic peptide level, ImmuKnow, and Allomap scores had negative relationships with the expression of mitochondria-related modules and positive relationships with immune-response modules.

Conclusions: During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment.

Citing Articles

Out of the ice age: Preservation of cardiac allografts with a reusable 10 °C cooler.

Trahanas J, Harris T, Petrovic M, Dreher A, Pasrija C, DeVries S JTCVS Open. 2024; 21:197-209.

PMID: 39534335 PMC: 11551297. DOI: 10.1016/j.xjon.2024.08.005.

Unsupervised mRNA-seq classification of heart transplant endomyocardial biopsies.

Romero E, Tabak E, Fishbein G, Litovsky S, Tallaj J, Liem D Clin Transplant. 2023; 37(9):e15011.

PMID: 37151104 PMC: 10524567. DOI: 10.1111/ctr.15011.

Microvesicular Steatosis and Severe Cardiac Allograft Dysfunction.

Mai X, Alvarez P, Rodriguez E, Tan C, Boyle G Transplant Direct. 2022; 8(3):e1290.

PMID: 35187215 PMC: 8843365. DOI: 10.1097/TXD.0000000000001290.

Human myocardial mitochondrial oxidative capacity is impaired in mild acute heart transplant rejection.

Scheiber D, Zweck E, Albermann S, Jelenik T, Spieker M, Bonner F ESC Heart Fail. 2021; 8(6):4674-4684.

PMID: 34490749 PMC: 8712779. DOI: 10.1002/ehf2.13607.

Mitochondrial Consequences of Organ Preservation Techniques during Liver Transplantation.

Horvath T, Jasz D, Barath B, Poles M, Boros M, Hartmann P Int J Mol Sci. 2021; 22(6).

PMID: 33802177 PMC: 7998211. DOI: 10.3390/ijms22062816.

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