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Integrative Omics Reveals Subtle Molecular Perturbations Following Ischemic Conditioning in a Porcine Kidney Transplant Model

ABSTRACT: Integrative Omics Reveals Subtle Molecular Perturbations Following Ischemic Conditioning in a Porcine Kidney Transplant Model

PROVIDER: PRJEB47176 | ENA |

REPOSITORIES: ENA

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Integrative Omics Reveals Subtle Molecular Perturbations Following Ischemic Conditioning in a Porcine Kidney Transplant Model

Project description:Background: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the Ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods: Kidney pairs (n = 8+8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed a modern integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results: In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. Conclusions: Our data identifies subtle molecular phenotypes in porcine kidneys following RIC and this knowledge could potentially aid optimisation of remote ischaemia protocols in renal transplantation.

2021-09-04 | E-MTAB-10872 | biostudies-arrayexpress

Transplant Model Ischemic Conditioning Causes Tissue Leakage and Suppressed Inflammation in a Porcine Kidney

Project description:Background: Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the Ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods: Kidney pairs (n = 8+8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One kidney in each pair was subjected to RIC prior to reperfusion, while the other served as non-RIC control. We designed an advanced integrative -Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results: In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, but more pronounced effects at the proteome level. In particular, we noted that RIC resulted in response suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in RIC tissues was detected at the protein level, which may result in response to muscle tissue damage and/or fibrosis. Conclusions: Our data identifies subtle molecular phenotypes in porcine kidneys subjected to RIC which could aid further optimisation of remote ischaemia protocols in renal transplantation.

2022-04-04 | PXD025273 | Pride

Expression data from plasma exosomal microRNA of rats with remote ischemic conditioning and normal controls

Project description:Remote ischemic conditioning (RIC) is a safely therapeutic strategy for a variety of ischemic diseases, with efficiency comparable to the classic in-situ ischemic methods. Recent evidence has shown that RIC could alter the content of circulating exosomes. microRNAs involves in numerous functionally different biological and physiological processes. The aim of this study is to identify the differentially expressed exosomal microRNAs in rat plasma with RIC and to further explore the functions in ischemic heart diseases. Five RIC rats and 5 control rats were enrolled in this study. We used microarray analysis to identify miRNA expression in their plasma exosomes.

2022-04-01 | GSE198747 | GEO

Proteomic analysis identifies plasma correlates of remote ischemic conditioning in the context of experimental traumatic brain injury

Project description:Remote ischemic conditioning (RIC) treatment has been shown to modify levels of traumatic brain injury (TBI) pathology related proteins, however, the mechanism is not widely understood. This study utilized LC-MS/MS to identify protein biomarkers of RIC treatment after TBI in mouse models.

2021-06-03 | PXD020420 | Pride

Pre-transplant conditioning propagates selective loss of host Helios+/Nrp1+ Treg in aHSCT

Project description:Comparative analysis of four murine Treg subsets differentially affected by pre-transplant conditioning and acute gastrointestinal GvHD following allogeneic hematopoietic stem cell transplantation.

2023-03-27 | GSE227929 | GEO

Untargeted Metabolomics Reveals a Mild Impact of Remote Ischemic Conditioning on the Plasma Metabolome and α-Hydroxybutyrate as a Possible Cardioprotective Factor and Biomarker of Tissue Ischemia

Project description:Remote ischemic conditioning (RIC) is a maneuver by which short non-lethal ischemic events are applied on distant organs or limbs to reduce ischemia and reperfusion injuries caused by e.g. heart attacks. As RIC can be induced using a simple blood pressure cuff e.g. prior to revascularization, it constitutes an easily applicable, safe and low-cost intervention to limit these injuries. Although intensively investigated, the specific mechanism of this protective phenomenon remains incompletely understood. Likewise, the identity of circulating factors, presumed to be involved in the initiation of protection, is unknown. In this study, we aimed to study perturbations in the plasma metabolome following RIC and gain insight into metabolic changes by the intervention as well as to identify potential novel cardio-protective metabolites. Blood plasma samples from 10 healthy males were collected prior to and after RIC and analyzed using untargeted LC-qTOF-MS. The analysis revealed a moderate impact on the plasma metabolome following RIC. However, one metabolite, α-hydroxybutyrate (AHB), stood out as highly significantly upregulated after RIC. AHB might be a novel and more sensitive plasma-biomarker of transient tissue ischemia than lactate. Importantly, it was also found that a cell permeable AHB precursor protects cardiomyocytes from ischemia-reperfusion damage.

2016-12-20 | MTBLS414 | MetaboLights

Expression data from plasma exosomal microRNA of rats with remote ischemic conditioning and normal controls

Project description:Expression data from plasma exosomal microRNA of rats with remote ischemic conditioning and normal controls

| PRJNA816728 | ENA

air-conditioning system dust

Project description:air-conditioning system dust Other

| PRJNA488116 | ENA

Gene expression changes in the periventricular white matter of neonatal piglets at a defined 48h time point following a hypoxic-ischemic insult: a comparison of piglets left untreated and those treated with a remote post-conditioning stimulus applied to the hind leg immediately after the insult.

Project description:Remote ischemic postconditioning (RIPostC) is a promising therapeutic intervention whereby brief episodes of ischemia/reperfusion of one organ (limb) mitigate damage in another organ (brain) that has experienced severe hypoxia-ischemia. 16 Large White newborn female piglets were exposed to a tightly controlled hypoxic-ischemic insult using magnetic resonance spectroscopy (MRS) biomarkers. After hypoxia-ischemia (HI), piglets were randomized to: (i) no intervention (nâ=â8); (ii) RIPostC â with four, 10-min cycles of bilateral lower limb ischemia/reperfusion immediately after HI (nâ=â8). Piglets in the remote post-conditioned group exhibited a reduction in white matter proton MRS lactate/N acetyl aspartate and increased whole brain phosphorus-31 MRS ATP over the 48âh after hypoxia-ischemia. Cell death (apoptosis) was reduced with RIPostC in the periventricular white matter, internal capsule and corpus callosum. There was also reduced microglial activation in corpus callosum and more surviving oligodendrocytes in corpus callosum and periventricular white matter. Our results demonstrate changes in the expression of 74 genes in the periventricular white matter 63 were down regulated and 11 were upregulated, that accompany the reductions in cell death and microglial activation seen following a remote post conditioning stimulus at a single 48h time point. (significance was calculated at p<0.05, one way ANOVA, Mann-Whitney unpaired, noe were found to be significant following a Benjamini-Hochberg FDR multipe testing correction). Many of these genes are thought to be important for the mediation of the neuroprotective effects of post-conditioning which suggests its genomic effects may persist for 48h. A full description of this work can be accessed at doi: 10.1177/0271678X15608862.

2016-09-21 | E-MTAB-5125 | biostudies-arrayexpress