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Major surgery induces acute changes in DNA methylation associated with immune response pathways

ABSTRACT: Major surgery induces acute changes in DNA methylation associated with immune response pathways

PROVIDER: PRJNA597341 | ENA |

REPOSITORIES: ENA

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Major surgery induces acute changes in DNA methylation associated with immune response pathways

Project description:Using a longitudinal study design, we quantified DNA methylation across the genome in a cohort of 30 elderly patients (average age = 77.9 years (range 62-91)) undergoing major surgery (either elective colorectal surgery, elective hip replacement surgery, and emergency hip surgery following fracture). From each individual, detailed clinical blood measures were collected and DNA methylation was profiled using the Illumina Human Methylation 450 array (g450K arrayh) (Illumina Inc. San Diego, California) in DNA samples isolated from purified PBMCs collected at three time-points: i) immediately before surgery (baseline (BL)), ii) in the morning of post-operative day 1 (POD1) and iii) between post-operative day 4 and 7 (POD4/7) prior to discharge from hospital.

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Major surgery induces acute changes in measured DNA methylation associated with immune response pathways.

Project description:Surgery is an invasive procedure evoking acute inflammatory and immune responses that can influence risk for postoperative complications including cognitive dysfunction and delirium. Although the specific mechanisms driving these responses have not been well-characterized, they are hypothesized to involve the epigenetic regulation of gene expression. We quantified genome-wide levels of DNA methylation in peripheral blood mononuclear cells (PBMCs) longitudinally collected from a cohort of elderly patients undergoing major surgery, comparing samples collected at baseline to those collected immediately post-operatively and at discharge from hospital. We identified acute changes in measured DNA methylation at sites annotated to immune system genes, paralleling changes in serum-levels of markers including C-reactive protein (CRP) and Interleukin 6 (IL-6) measured in the same individuals. Many of the observed changes in measured DNA methylation were consistent across different types of major surgery, although there was notable heterogeneity between surgery types at certain loci. The acute changes in measured DNA methylation induced by surgery are relatively stable in the post-operative period, generally persisting until discharge from hospital. Our results highlight the dramatic alterations in gene regulation induced by invasive surgery, primarily reflecting upregulation of the immune system in response to trauma, wound healing and anaesthesia.

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Normalization of adipose oxidative metabolism pathways after bariatric surgery

Project description:The molecular background of mitochondrial dysfunction in adipose tissue of morbidly obese individuals and bariatric surgery-induced changes in adipose mitochondrial function remain incompletely understood. To evaluate the mechanisms behind the surgery-induced changes and differences between morbidly obese subjects and nonobese controls, we performed a LC-MS/MS proteomics analysis of abdominal subcutaneous (SAT) and visceral adipose tissue samples (VAT) collected from the bariatric surgery, SAT samples collected 6 months after surgery, and control SAT and VAT samples collected from baseline.

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Bariatric surgery induces long-term changes on the gut metagenome contributing to fat mass regulation

Project description:Bariatric surgery induces long-term changes on the gut metagenome contributing to fat mass regulation

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Longitudinal Profiling in Patients Undergoing Cardiac Surgery Reveals Postoperative Changes in DNA Methylation

Project description:Cardiac surgery and cardiopulmonary bypass induce a substantial immune and inflammatory response, the overactivation of which is associated with significant complications. Longitudinal DNA methylation profiling allows the potential to identify changes in gene regulatory mechanisms that are secondary to surgery and to identify molecular processes that predict and/or cause postoperative complications. In this study, we measure DNA methylation in preoperative and postoperative whole blood samples from 96 patients undergoing cardiac surgery on cardiopulmonary bypass. We identify several loci with statistically significant postoperative changes in methylation. Additionally, two of these loci are associated with new-onset postoperative atrial fibrillation, a significant complication after cardiac surgery. This research establishes that there are statistically significant changes in DNA methylation that occur immediately after cardiac surgery and that these acute alterations in DNA methylation have the granularity to identify processes associated with major postoperative complications.

2023-01-09 | GSE215937 | GEO

Acute phase serum proteome in Cardiac Surgery

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.

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Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes

Project description:Bariatric surgery is highly effective for the treatment of obesity in individuals without (OB ) and in those with type 2 diabetes (T2D ). However, whether bariatric surgery triggers similar or distinct molecular changes in OB and T2D remains unknown. Given that individuals with type 2 diabetes often exhibit more severe metabolic deterioration, we hypothesized that bariatric surgery induces distinct molecular adaptations in skeletal muscle, the major site of glucose uptake, of OB and T2D after surgery-induced weight loss. All participants (OB, n=13; T2D, n=13) underwent detailed anthropometry before and one year after the surgery. Skeletal muscle biopsies were isolated at both time points and subjected to transcriptome and methylome analyses using a comprehensive bioinformatic pipeline.

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Changes in cardiac transcription profiles following off-pump coronary revascularization surgery

Project description:To investigate changes in cardiac transcription profiles caused by off-pump cardiac surgery, we collected myocardial samples, prior and after grafting, from patients undergoing off-pump coronary revascularization surgery. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Changes in transcriptional profiles can be correlated with the stress response of heart to off-pump surgery. Keywords: human, cardiac, OPCAB coronary surgery, gene expression.

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