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Circulating mitochondrial genes detect acute cardiac allograft rejection: Role of the mitochondrial calcium uniporter complex
Author(s) -
Tarazón Estefanía,
PérezCarrillo Lorena,
GarcíaBolufer Pau,
Triviño Juan C.,
FeijóoBandín Sandra,
Lago Francisca,
GonzálezJuanatey José R.,
MartínezDolz Luis,
Portolés Manuel,
RosellóLletí Esther
Publication year - 2021
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.16387
Subject(s) - uniporter , medicine , receiver operating characteristic , mitochondrion , transplantation , area under the curve , heart transplantation , cardiology , biology , microbiology and biotechnology , biochemistry , cytosol , enzyme
Acute rejection after heart transplantation increases the risk of chronic dysfunction. Disturbances in mitochondrial function may play a contributory role, however, the relationship between histological signs of rejection in the human transplanted heart and expression levels of circulating mitochondrial genes, such as the mitochondrial Ca 2+ uniporter (MCU) complex, remains unexplored. We conducted an RNA‐sequencing analysis to identify altered mitochondrial genes in serum and to evaluate their diagnostic accuracy for rejection episodes. We included 40 consecutive samples from transplant recipients undergoing routine endomyocardial biopsies. In total, 112 mitochondrial genes were identified in the serum of posttransplant patients, of which 28 were differentially expressed in patients with acute rejection ( p < .05). Considering the receiver operating characteristic analysis with an area under the curve (AUC) >0.900 to discriminate patients with moderate or severe degrees of rejection, we found that the MCU system showed a strong capability for detection: MCU (AUC = 0.944, p < .0001), MCU / MCUR1 ratio (AUC = 0.972, p < .0001), MCU / MCUB ratio (AUC = 0.970, p < .0001), and MCU / MICU1 ratio (AUC = 0.970, p < .0001). Mitochondrial alterations are reflected in peripheral blood and are capable of discriminating between patients with allograft rejection and those not experiencing rejection with excellent accuracy. The dysregulation of the MCU complex was found to be the most relevant finding.