Project description:We report on the application of RNA sequencing to study expression changes in cardiac surgery patients of different obesity categories.
Project description:Anesthetic gases elicit organ protection in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed at identifying myocardial transcriptional phenotypes and anesthetic-induced changes in gene expression to predict cardiovascular biomarkers and cardiac function after off-pump CABG. Keywords: cardiac surgery, anesthetics
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.
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. Myocardial samples were collected, prior and after grafting, from patients undergoing off-pump coronary artery bypass grafting.
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.
Project description:Acute kidney injury (AKI) associated with cardiac surgery may increase mortality and incidence rate of chronic kidney disease in critically ill patients. One purpose of this study was to investigate the possible correlations between urinary proteomic changes and cardiac surgery-related AKI.
Project description:Lysine residues undergo diverse and reversible post-translational modifications including acetylation. Acetylation of lysine residues have traditionally been studied as epigenetic modifiers of histone tails within chromatin that provides an important mechanism for regulating gene expression. In the heart, histone acetylation acts as a key regulator of cardiac remodeling and function. However, recent studies have shown that thousands of proteins (~4,500) can be acetylated at multiple acetylation sites (~15,000 sites). These data suggest that the acetylome rivals phosphorylation in prevalence as a post-translational modification. Based on this, we examined the impact of obesity on the regulation of lysine acetylation in the left ventricle of male c57BL/6J mice. We report that obesity contributed to a significant increase in heart enlargement and fibrosis. Of interest, immunoblot analysis demonstrated that lysine acetylation was markedly altered in response to diet-induced obesity and that this phenomena was cardiac tissue specific. Mass spectral analysis was performed in which 3264 proteins were identified in the left ventricle. Of these, 254 proteins were acetylated, 16 of which were significantly impacted by obesity. Ingenuity Pathway Analysis identified the Cardiovascular Disease network as significantly regulated by obesity, 54 of the 254 acetylated proteins impact this pathway. This network includes LIM domain-binding protein 3 (LDB3), aconitate hydratase (ACO2), and dihydrolipoyl dehydrogenase (DLD), which are all significantly impacted by obesity and known to regulate cardiac function. Combined, these findings suggest a critical role for the cardiac acetylome in obesity-mediated remodeling and ultimately have the potential to elucidate novel targets that regulate cardiac pathology.
Project description:Objectives: Secretion of extracellular vesicles (EV) and associated micro-RNAs (miR) is altered during cellular stress and may serve as biomarkers of organ injury. We hypothesized that measuring changes in urinary levels of EV and miR will predict the onset of acute kidney injury in cardiac surgery patients. Design: Predictive accuracy biomarker study performed in the cohort of the REVAKI-2 trial Setting: Single center ICU between September 2015 and September 2018 Interventions: Intravenous sildenafil citrate 12.5 mg kg-1 over 150 min or dextrose 5% at the commencement of surgery. Measurements and main results: Urine samples were collected before and 24 hours after the procedure from 93 cardiac surgery patients. Urine EV concentrations and size distribution were assessed using NanoSight. EV derivation and levels were measured using flow cytometry. Samples from 10 selected patients were sequenced to detect differentially expressed miR. Verification was performed with advanced TaqMan assays in samples from all patients. Urine EV concentrations significantly increased in patients with AKI after surgery, with the percentage of EV positive for aquaporin-2 and β1-integrin also increasing. Pre surgery podocalyxin-positive EV were significantly lower, and β1-integrin EV werehigher in patients with AKI. The levels of the former correlated with the severity of theinjury. miR-125a-5p was expressed at higher levels in urine from patients with AKI stage 2/3. Levels of miR-10a-5p decreased after surgery in AKI patients; its levels correlated with the severity of the injury. Preoperative levels of podocalyxin EVs and miR-125a-5p had moderate AKI predictive value and, in a logistic model together with ICU lactate levels, offered good (AUC = 80.9%) AKI prediction. Conclusions: Lower levels of podocalyxin-positive EV at baseline predict the severity of post-surgery AKI. Urine EV concentrations and miR expression offer excellent predictive accuracy when combined with commonly measured biomarkers.
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.
Project description:Study aims to identify circulating small RNAs that report early heart injury after cardiac surgery with a view to translating them to the early diagnosis of myocardial infarction