Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats

Lin, Feng; Ou, Yi; Huang, Chuanbing; Lin, Shengzhe; Ye, Yunbin

doi:10.1038/s41598-017-15761-3

Cited by 6 publications

(4 citation statements)

References 59 publications

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“…D-glutamine exhibited good diagnostic capability for the diagnosis of the early acute rejection after heart transplantation with a high sensitivity and specificity. 38 Moreover, inhibition of glutamine metabolism was considered to prevent graft rejection by inhibiting generation and function of effector T cells. In fully mismatched skin and heart allograft transplantation models, the inhibitor of glutamine metabolism 6-diazo-5-oxo-L-norleucine (DON) combined with the glycolytic inhibitor 2-deoxyglucose (2-DG) and the anti-type II diabetes drug metformin, were demonstrated to prevent or delay graft rejection.…”

Section: Discussionmentioning

confidence: 99%

Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection

Wang¹,

Zhang²,

Li³

et al. 2023

TCRM

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Background Antibody-mediated rejection (AMR) is emerging as the main cause of graft loss after kidney transplantation. Our previous study revealed the gut microbiota alternation associated with AMR in kidney transplant recipients, which was predicted to affect the metabolism-related pathways. Methods To further investigate the shifts in intestinal metabolic profile among kidney transplantation recipients with AMR, fecal samples from kidney transplant recipients and patients with end-stage renal disease (ESRD) were subjected to untargeted LC-MS-based metabolomics. Results A total of 86 individuals were enrolled in this study, including 30 kidney transplantation recipients with AMR, 35 kidney transplant recipients with stable renal function (KT-SRF), and 21 participants with ESRD. Fecal metabolome in patients with ESRD and kidney transplantation recipients with KT-SRF were parallelly detected as controls. Our results demonstrated that intestinal metabolic profile of patients with AMR differed significantly from those with ESRD. A total of 172 and 25 differential metabolites were identified in the KT-AMR group, when compared with the ESRD group and the KT-SRF group, respectively, and 14 were common to the pairwise comparisons, some of which had good discriminative ability for AMR. KEGG pathway enrichment analysis demonstrated that the different metabolites between the KT-AMR and ESRD groups or between KT-AMR and KT-SRF groups were significantly enriched in 33 or 36 signaling pathways, respectively. Conclusion From the metabolic point of view, our findings may provide key clues for developing effective diagnostic biomarkers and therapeutic targets for AMR after kidney transplantation.

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Section: Discussionmentioning

confidence: 99%

Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection

Wang¹,

Zhang²,

Li³

et al. 2023

TCRM

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“…Lin et al (2017) recently used a heterotopic HTx rat model to determine the metabolic profile post-BSD in serum. 136 They found a panel of 4 metabolites, D-tagatose, choline, C16 sphinganine and D-glutamine, could accurately diagnose early rejection.…”

Section: A C C E P T E Dmentioning

confidence: 99%

“…Future studies profiling these changes in myocardium and biofluids with thorough biochemical techniques (eg metabolomics, magnetic resonance imaging), across acute and chronic post-HTx stages are necessary to ascertain therapeutic targets and the metabolic state of the transplanted heart. Targeting aberrant signalling, altering metabolic function (as in those studies on HF 35 ) or identifying risk of graft failure via metabolic biomarkers such as those identified by Lin et al 136 , or the panel of metabolites identified in liver 10 and kidney transplant 11,12 studies, may thus improve patient outcomes.…”

Section: A C C E P T E Dmentioning

confidence: 99%

Peritransplant Cardiometabolic and Mitochondrial Function: The Missing Piece in Donor Heart Dysfunction and Graft Failure

et al. 2021

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Primary graft dysfunction (PGD) is an important cause of morbidity and mortality after cardiac transplantation. Donor brain stem death (BSD) is a significant contributor to donor heart dysfunction (DHD) and PGD. There remain substantial gaps in the mechanistic understanding of peritransplant cardiac dysfunction. One of these gaps is cardiac metabolism and metabolic function. The healthy heart is an 'omnivore', capable of utilising multiple sources of nutrients to fuel its enormous energetic demand. When this fails, metabolic inflexibility leads to myocardial dysfunction. Data have hinted at metabolic disturbance in the BSD donor and subsequent HTx, however, there is limited evidence demonstrating specific metabolic or mitochondrial dysfunction. This review will examine the literature surrounding cardiometabolic and mitochondrial function in the BSD donor, organ preservation, and subsequent cardiac transplantation. A more comprehensive understanding of this subject may then help to identify important cardioprotective strategies to improve the number and quality of donor hearts.

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“…Moreover, MS can also be combined with chromatographic methods (LC or GS) to improve metabolite separation. These technologies allow the investigation of metabolic changes in disease models and organ physiology, including Tx [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Metabolomics in Current Concepts of Organ Preservation

Kvietkauskas

Zitkute

Leber

et al. 2020

IJMS

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In solid organ transplantation (Tx), both survival rates and quality of life have improved dramatically over the last few decades. Each year, the number of people on the wait list continues to increase, widening the gap between organ supply and demand. Therefore, the use of extended criteria donor grafts is growing, despite higher susceptibility to ischemia-reperfusion injury (IRI) and consecutive inferior Tx outcomes. Thus, tools to characterize organ quality prior to Tx are crucial components for Tx success. Innovative techniques of metabolic profiling revealed key pathways and mechanisms involved in IRI occurring during organ preservation. Although large-scale trials are needed, metabolomics appears to be a promising tool to characterize potential biomarkers, for the assessment of graft quality before Tx and evaluate graft-related outcomes. In this comprehensive review, we summarize the currently available literature on the use of metabolomics in solid organ Tx, with a special focus on metabolic profiling during graft preservation to assess organ quality prior to Tx.

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Metabolomics identifies metabolite biomarkers associated with acute rejection after heart transplantation in rats

Cited by 6 publications

References 59 publications

Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection

Shifts in Intestinal Metabolic Profile Among Kidney Transplantation Recipients with Antibody-Mediated Rejection

Peritransplant Cardiometabolic and Mitochondrial Function: The Missing Piece in Donor Heart Dysfunction and Graft Failure

The Role of Metabolomics in Current Concepts of Organ Preservation

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