MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study.
Acute Coronary Syndrome
/ blood
Aged
Case-Control Studies
Chromosome Mapping
Elective Surgical Procedures
/ adverse effects
Extracellular Matrix
/ chemistry
Female
Heart Injuries
/ blood
Humans
Male
Metabolic Networks and Pathways
MicroRNAs
/ blood
Middle Aged
Myocardial Ischemia
/ blood
Postoperative Complications
/ blood
Prospective Studies
microRNA
noncardiac surgery
perioperative myocardial injury
perioperative period
postoperative complications
Journal
British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
02
03
2020
revised:
08
05
2020
accepted:
31
05
2020
pubmed:
29
7
2020
medline:
11
11
2020
entrez:
29
7
2020
Statut:
ppublish
Résumé
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. 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). 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. Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.
Sections du résumé
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.
Identifiants
pubmed: 32718726
pii: S0007-0912(20)30509-2
doi: 10.1016/j.bja.2020.05.066
pmc: PMC7678162
pii:
doi:
Substances chimiques
MicroRNAs
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
661-671Subventions
Organisme : Medical Research Council
ID : MR/M017974/1
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.
Références
EMBO Mol Med. 2012 Nov;4(11):1176-85
pubmed: 23023917
Nat Rev Mol Cell Biol. 2019 Jan;20(1):5-20
pubmed: 30228348
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12011-6
pubmed: 17620599
Bioinformatics. 2006 Jul 1;22(13):1600-7
pubmed: 16606683
J Mol Cell Cardiol. 2016 Dec;101:127-133
pubmed: 27832939
Br J Anaesth. 2020 May;124(5):535-543
pubmed: 32147104
BMJ. 2015 Apr 22;350:h1907
pubmed: 25902738
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Int J Clin Exp Med. 2014 Jan 15;7(1):136-41
pubmed: 24482699
Clin Chem. 2010 Jul;56(7):1183-5
pubmed: 20395621
RNA. 2008 May;14(5):844-52
pubmed: 18375788
Br J Anaesth. 2019 Feb;122(2):188-197
pubmed: 30686304
Cardiovasc Res. 2020 May 1;116(6):1113-1124
pubmed: 31782762
Nucleic Acids Res. 2015 Jul 1;43(W1):W460-6
pubmed: 25977294
Nucleic Acids Res. 2019 Jan 8;47(D1):D155-D162
pubmed: 30423142
Acta Physiol (Oxf). 2007 Jun;190(2):127-36
pubmed: 17394575
Anesthesiology. 2014 Mar;120(3):564-78
pubmed: 24534856
J Physiol. 2015 Mar 15;593(6):1361-82
pubmed: 25772291
Cancer Res. 2004 Aug 1;64(15):5245-50
pubmed: 15289330
Clin Chem. 2009 Apr;55(4):611-22
pubmed: 19246619
Bioinformatics. 2019 Feb 1;35(3):421-432
pubmed: 30020410
Circ Res. 2014 Feb 14;114(4):689-705
pubmed: 24526675
Nat Rev Cardiol. 2014 May;11(5):255-65
pubmed: 24663091
Circ Res. 2011 Jan 21;108(2):219-34
pubmed: 21252150
Eur Heart J. 2010 Mar;31(6):659-66
pubmed: 20159880
Circ Res. 2012 Feb 3;110(3):483-95
pubmed: 22302755
PLoS One. 2014 Feb 12;9(2):e88566
pubmed: 24533109
Nucleic Acids Res. 2013 Jan;41(Database issue):D991-5
pubmed: 23193258
Circulation. 2011 Nov 1;124(18):1936-44
pubmed: 21969012
BMC Bioinformatics. 2011 Mar 17;12:77
pubmed: 21414208
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
J Mol Cell Cardiol. 2016 May;94:107-121
pubmed: 27056419
Nat Cell Biol. 2007 Jun;9(6):654-9
pubmed: 17486113
Methods. 2013 Jan;59(1):S1-6
pubmed: 23036329
Br J Anaesth. 2019 Feb;122(2):180-187
pubmed: 30686303
Science. 2007 Apr 27;316(5824):575-9
pubmed: 17379774
Lancet. 2018 Jun 30;391(10140):2631-2640
pubmed: 30070222
Circ Cardiovasc Genet. 2010 Dec;3(6):499-506
pubmed: 20921333
Br J Anaesth. 2019 Dec;123(6):758-767
pubmed: 31492527
J Mol Cell Cardiol. 2011 Nov;51(5):872-5
pubmed: 21806992
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12481-6
pubmed: 16885212
Cardiovasc Res. 2016 Sep;111(4):322-37
pubmed: 27357636
Nucleic Acids Res. 2009 Apr;37(6):e45
pubmed: 19237396
Int Heart J. 2016 May 25;57(3):350-5
pubmed: 27181040