Shaun M May1, Tom E F Abbott1, Ana G Del Arroyo1, Anna Reyes2, Gladys Martir2, Robert C M Stephens2, David Brealey2, Brian H Cuthbertson3, Duminda N Wijeysundera4, Rupert M Pearse1, Gareth L Ackland5. 1. Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. 2. University College London NHS Hospitals Trust, London, UK. 3. Department of Anaesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada; Department of Critical Care Medicine, Sunnybrook Health Science Centre, Toronto, ON, Canada. 4. Department of Anaesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. 5. Translational Medicine & Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address: g.ackland@qmul.ac.uk.
Abstract
BACKGROUND: Elevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. METHODS: We performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). RESULTS: MicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia. CONCLUSIONS: Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury. Crown
BACKGROUND: Elevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. METHODS: We performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRT-PCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). RESULTS: MicroRNAs were detectable in all 59 patients (median age 67 yr [61-75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95-8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94-10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n=48) and two (n=11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia. CONCLUSIONS: Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury. Crown
Authors: Omid Shirvani Samani; Johannes Scherr; Elham Kayvanpour; Jan Haas; David H Lehmann; Weng-Tein Gi; Karen S Frese; Rouven Nietsch; Tobias Fehlmann; Steffi Sandke; Tanja Weis; Andreas Keller; Hugo A Katus; Martin Halle; Norbert Frey; Benjamin Meder; Farbod Sedaghat-Hamedani Journal: J Clin Med Date: 2021-12-21 Impact factor: 4.241
Authors: Robert D Sanders; Lenka Craigova; Benjamin Schessler; Cameron Casey; Marissa White; Margaret Parker; David Kunkel; Kaj Blennow; Henrik Zetterberg; Robert A Pearce; Richard Lennertz Journal: Br J Anaesth Date: 2020-11-04 Impact factor: 9.166