Transcriptomic Analysis of Circulating Extracellular Vesicles and Serum during the Perioperative period of Fontan and Glenn Surgery
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PROVIDER: PRJNA1124062 | ENA |
REPOSITORIES: ENA
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Project description:Single-ventricle defects are palliatively corrected using the Glenn and Fontan procedures that provide lifesaving relief but lead to early mortality rates and poor prognosis post-operatively. The pathophysiology of these complications is diverse, and there are no clear predictors for these outcomes. As such, we aimed to identify novel biomarkers for single-ventricle associated outcomes through the characterization of the serum transcriptome and small extracellular vesicles (sEVs). We report on molecular responses in serum and sEVs pre-operatively and post-operatively in patients undergoing either Glenn or Fontan operations. We found that transcriptomes of serum RNA and sEV RNA are distinctly different, whereas differences between the Fontan and Glenn transcriptomes did not show any significant changes. An in vitro wound healing assay further confirmed that post-operative sEVs have higher angiogenic potential. Moreover, we used a partial-least square regression model to identify 100 RNAs and 50 microRNAs that are involved in angiogenesis-related pathways and accurately predict our wound healing results and compared them with our previously published models of ovine Fontan surgery. Lastly, an EV-origin analysis showed decreased secretion of sEV from cardiac tissue in post-operative samples and increased secretion of sEVs from stomach and nervous tissue. Overall, this study provided evidence that the circulating sEVs transcriptome are potent biomarkers and demonstrated the role of sEVs as a possible mediator for formation of veno-venous collaterals.
2024-12-20 | GSE269879 | GEO
Project description:There are no curative treatment options for patients with single ventricle disease. Rather, the standard of care includes a series of palliative procedures that culminate in the Fontan operation, which, while life-saving, nevertheless reduces longevity and quality of life. The cause of late term death in these patients is typically ascribed to insidious end organ sequelae associated with the Fontan circulation. The etiology underlying these pathological processes remains unknown, but is thought to be diverse and multifactorial, arising from progressive deterioration of end-organ function due to the non-physiologic Fontan hemodynamics and its consequences on tissue perfusion and remodeling.Our overall goal is to evaluate the impact of Fontan physiology on cardiopulmonary remodeling over long periods in an ovine Fontan survival model.
2022-12-30 | GSE201288 | GEO
Project description:This study is an analysis of the Bern perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass at Bern University Hospital between January and December 2019. Blood samples were taken at induction of anaesthesia and on postoperative day one.
2023-11-27 | PXD046496 | Pride
Project description:Background On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia–reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. Methods We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia–reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia–reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. Findings In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32–0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68–0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning–afternoon variation in hypoxia–reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia–reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia–reperfusion injury modulator CDKN1a/p21. Interpretation Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery.
2018-03-03 | GSE111351 | GEO
Project description:Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery
| PRJNA830752 | ENA
Project description:Elevated NLR (neutrophil-lymphocyte ratio) in elective vascular surgery (EVS) patients is associated with increased mortality independent of perioperative surgical outcome. To understand why high NLR is associated with higher mortality, we investigated neutrophil and lymphocyte transcriptome expression in patients undergoing EVS.
2022-08-17 | GSE211190 | GEO
Project description:The incidence of perioperative neurocognitive disorders (PND) is high, especially after cardiac surgeries, and the underlying mechanisms remain elusive. Here, we conducted a prospective observational study to observe serum proteomics differences in PND patients after cardiac valve replacement surgery.
2024-01-23 | PXD048818 |
Project description:Perioperative neurocognitive dysfunction (PND) is emerging as a significant complication of surgery in elderly patients. However, the molecular mechanisms of PND are not well known. Here we applied microarray analysis to identify circular RNAs (circRNAs) in hippocampus from a mouse model of PND and control mice. Then, the dysregulated circRNAs were confirmed via quantitative real-time polymerase chain reaction (qRT-PCR). Then, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to probe the vital functions of dysregulated genes.
2021-08-10 | GSE165798 | GEO
Project description:Background: Perioperative neurocognitive disorders (PND), a postoperative cognitive dysfunction occurs more often in the elderly. The etiology of PND remains largely elusive. This study aims to understand the etiology in a mouse model with tibial fracture (a surgical trauma), by examining the transcriptome-wide response of hippocampus, a brain region that is tightly associated with memory formation. Methods: Mice at age of 7~8 months were randomly divided into two groups, surgery (tibial fracture) group and control (sham) group. At day (d) 1 after the surgical operation, hippocampal tissues were isolated and then subjected to RNA extraction and RNA sequencing (RNA-seq). Findings: Levels of respiratory complex related genes are significantly decreased in the brain of mice subjected to surgery. Consequently, the activities of multiple respiratory complexes and respiratory chain function is decreased in the hippocampus of mice with surgical operation. Interpretation: We here propose a novel mechanism of mitochondrial dysfunction in PND etiology, and also provide a potential therapeutic target for PND.
2022-02-09 | GSE178995 | GEO
Project description:Denutrition and Obesity are risk factors for perioperative surgical complications.
In patient with cancer, incidence of denutrition is markedly increased. Surgical resection of cancer induces a high intensity cellular stress response and catabolism reinforcing the risk for perioperative denutrition.
In this study, we thought to investigate the change in body composition during the perioperative period using anthropometric measurements and Bioelectrical Impedance Analysis (BIA).
| 2167014 | ecrin-mdr-crc