Epigenetics in the perioperative period

Lirk, Philipp; Fiegl, Heidi; Weber, Nina C.; Hollmann, Markus W.

doi:10.1111/bph.12865

Cited by 49 publications

(29 citation statements)

References 76 publications

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“…Cancer research has pioneered the study of epigenetic modifications that promote an immunosuppressed phenotype thereby facilitating immune evasion by cancerous cells and has also been at the forefront of developing epigenetic modifying agents that can target these processes [53*]. In the perioperative period epigenetic studies have largely focused on acute and chronic pain processes, although data supportive of a key role in inflammation and immunosuppression have emerged [54]. For example, the use of opioids in the perioperative period promotes global DNA methylation in peripheral blood leukocytes [55].…”

Section: Epigenetics and Immune Responsivenessmentioning

confidence: 99%

The perioperative immune response

O’Dwyer

Owen

Torrance

2015

Current Opinion in Critical Care

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Purpose of ReviewA host of immune modulators are now available in clinical practice. The perioperative period is characterised by profound alterations in host immunity, which can result in poor outcomes, which include infection, cancer recurrence and organ failure. Manipulation of the peri-operative immune response has the potential to improve outcomes. A complete understanding of the mechanisms and clinical consequences of altered immune function in this setting is therefore imperative. Recent findingsRecent in vivo data has emerged which furthers our understanding of the interaction between tissue damage, immune modulation and clinical outcomes by utilising novel laboratory techniques capable of monitoring single cell immune signatures. Traditional gene expression assays have continued to demonstrate their utility and have been instrumental in defining the host response to perioperative allogeneic blood transfusion. These mechanistic studies are complemented by large clinical studies describing associations between anaesthetic modalities and immune-related outcomes. SummaryLaboratory techniques are now available that can monitor the perioperative immune response and could be further developed to introduce personalised care pathways. Consideration must also be given to anaesthesia techniques and perioperative treatments that, whilst not immediately harmful, may be associated with poor outcomes temporally distant from the treatment, secondary to induced immunosuppression.3

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Section: Epigenetics and Immune Responsivenessmentioning

confidence: 99%

The perioperative immune response

O’Dwyer

Owen

Torrance

2015

Current Opinion in Critical Care

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“…Thus miRNAs may be able to assist drug behaviour by altering its distribution of metabolism. Epigenetic drugs may assist not just in pharmacological therapy, but also in operations and pain management (Lirk et al, 2015). Nutrition can help any pharmacological therapy (Remely et al, 2015), indeed epigenetic mechanisms may assist in the mitochondrial adaptation necessary to counter type II diabetes (Henagan et al, 2015).…”

Section: Challengesmentioning

confidence: 99%

Epigenetics and pharmacology

Stefańska

MacEwan

2015

British J Pharmacology

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Recent advances in the understanding of gene regulation have shown there to be much more regulation of the genome than first thought, through epigenetic mechanisms. These epigenetic mechanisms are systems that have evolved to either switch off gene activity altogether, or fine-tune any existing genetic activation. Such systems are present in all genes and include chromatin modifications and remodelling, DNA methylation (such as CpG island methylation rates) and histone covalent modifications (e.g. acetylation, methylation), RNA interference by short interfering RNAs (siRNAs) and long non-coding RNAs (ncRNAs). These systems regulate genomic activity 'beyond' simple transcriptional factor inducer or repressor function of genes to generate mRNA. Epigenetic regulation of gene activity has been shown to be important in maintaining normal phenotypic activity of cells, as well as having a role in development and diseases such as cancer and neurodegenerative disorders such as Alzheimer's. Newer classes of drugs regulate epigenetic mechanisms to counteract disease states in humans. The reports in this issue describe some advances in epigenetic understanding that relate to human disease, and our ability to control these mechanisms by pharmacological means. Increasingly the importance of epigenetics is being uncovered -it is pharmacology that will have to keep pace. LINKED ARTICLESThis article is part of a themed section on Epigenetics and Therapy. To view the other articles in this section visit http://dx

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“…Furthermore, many different drugs are given not only in the operating room, but also for several days after surgery. Perioperative opiates and local anaesthetics also alter the level of DNA methylation (Bain & Shaw, ; Naguib, Bie, & Ting, ; Lirk et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, the cancer pathway has been associated with differential DNA methylation pattern induced by certain kinds of stressors, including obesity (Fradin et al, 2017), nonalcoholic steatohepatitis (de Mello et al, 2017), cigarette smoking (Sundar et al, 2017) and working night shifts (Adams et al, 2017), in addition to an epigenetic event in cancer itself. Surgery involves a complex reaction called the "surgical stress response" (Lirk et al, 2015), which is substantially similar to traumatic or burn injury and is mediated primarily by the hypothalamic-pituitary axis, resulting in the release of stress hormones (Finnerty, Mabvuure, Ali, Kozar, & Herndon, 2013). Genomic responses to stress encompass a broad range of inflammatory, immune and hormonal factors (Finnerty et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Factors, such as diet, obesity, physical activity, tobacco smoking, alcohol consumption, environmental pollutants and working night shifts potentially influence DNA methylation (Alegría‐Torres, Baccarelli, & Bollati, ). Because surgical techniques impart considerable stress on the human body, DNA methylation may, at least in part, determine an individuals’ reaction to the physiological changes induced by the surgery (Lirk, Fiegl, Weber, & Hollmann, ).…”

Section: Introductionmentioning

confidence: 99%

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Orthognathic surgery induces genomewide changes longitudinally in DNA methylation in saliva

et al. 2018

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Objective Orthognathic surgery dramatically changes morphology of the maxillofacial deformity and improves the malocclusion morphologically and functionally. We investigated the influence of orthognathic surgery on genomewide DNA methylation in saliva. Methods Saliva was obtained from nine patients undergoing orthognathic surgery and two healthy reference individuals before and 3 months after orthognathic surgery. Genomewide DNA methylation profiling of saliva (341,482 CpG dinucleotides) was conducted using Infinium HumanMethylation450 BeadChips. Results Comparison between pre‐ and postsurgery saliva samples revealed significant changes in DNA methylation patterns at 2,381 CpG sites (p < 0.01) with suggestive significance. The differentially methylated probe sets were significantly associated with the cancer pathway (p = 2.8 × 10−7; a false discovery rate q‐value = 3.7 × 10−4) and PI3K‐Akt signalling pathway (p = 2.4 × 10−5; a false discovery rate q‐value = 3.1 × 10−2). Conclusion Pathway enrichment analysis of genes with suggestive significance demonstrated that altered DNA methylation in saliva of patients undergoing orthognathic surgery, possibly as a response to surgical stress or bone injury. Further studies with a large sample size and long‐term observation are needed to validate the phenomena identified in this study.

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Epigenetics in the perioperative period

Cited by 49 publications

References 76 publications

The perioperative immune response

The perioperative immune response

Epigenetics and pharmacology

Orthognathic surgery induces genomewide changes longitudinally in DNA methylation in saliva

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