Cardiac transcriptional and metabolic changes following thoracotomy.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
15 06 2020
15 06 2020
Historique:
received:
06
12
2019
accepted:
29
04
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Non-cardiac surgery is associated with significant cardiovascular complications. Reported mortality rate ranges from 1.9% to 4% in unselected patients. A postoperative surge in pro-inflammatory cytokines is a well-known feature and putative contributor to these complications. Despite much clinical research, little is known about the biomolecular changes in cardiac tissue following non-cardiac surgery. In order to increase our understanding, we analyzed whole-transcriptional and metabolic profiling data sets from hearts of mice harvested two, four, and six weeks following isolated thoracotomy. Hearts from healthy litter-mates served as controls. Functional network enrichment analyses showed a distinct impact on cardiac transcription two weeks after surgery characterized by a downregulation of mitochondrial pathways in the absence of significant metabolic alterations. Transcriptional changes were not detectable four and six weeks following surgery. Our study shows distinct and reversible transcriptional changes within the first two weeks following isolated thoracotomy. This coincides with a time period, in which most cardiovascular events happen.
Identifiants
pubmed: 32541655
doi: 10.1038/s41598-020-66721-3
pii: 10.1038/s41598-020-66721-3
pmc: PMC7295769
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9673Références
Pearse, R. M. et al. Mortality after surgery in Europe: a 7 day cohort study. Lancet (London, England). 380, 1059–65 (2012).
doi: 10.1016/S0140-6736(12)61148-9
Devereaux, P. J. et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 307, 2295–304 (2012).
doi: 10.1001/jama.2012.5502
Devereaux, P. J. et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet (London, England). 371, 1839–47 (2008).
doi: 10.1016/S0140-6736(08)60601-7
Ni Choileain, N. & Redmond, H. P. Cell response to surgery. Arch. Surg. 141, 1132–40 (2006).
doi: 10.1001/archsurg.141.11.1132
Lindenauer, P. K., Pekow, P., Wang, K., Gutierrez, B. & Benjamin, E. M. Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery. JAMA. 291, 2092–9 (2004).
doi: 10.1001/jama.291.17.2092
Müller, O. J. et al. Comprehensive plasma and tissue profiling reveals systemic metabolic alterations in cardiac hypertrophy and failure. Cardiovasc. Res. 115, 1296–1305 (2019).
doi: 10.1093/cvr/cvy274
Lehmann, L. H. et al. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling. Proc. Natl. Acad. Sci. USA 111, 13499–504 (2014).
doi: 10.1073/pnas.1409026111
Heckmann, M. B. et al. AAV9-mediated gene transfer of desmin ameliorates cardiomyopathy in desmin-deficient mice. Gene Ther. 23, 673–9 (2016).
doi: 10.1038/gt.2016.40
R Core Team. R: A Language and Environment for Statistical Computing (2018).
Warnes, G. R. et al. gplots: Various R Programming Tools for Plotting Data (2016).
Yu, G., Wang, L.-G., Yan, G.-R. & He, Q.-Y. DOSE: an R/Bioconductor package for Disease Ontology Semantic and Enrichment analysis. Bioinformatics. 31, 608–609 (2015).
doi: 10.1093/bioinformatics/btu684
Yu, G. & He, Q.-Y. ReactomePA: an R/Bioconductor package for reactome pathway analysis and visualization. Mol. Biosyst. 12, 477–479 (2016).
doi: 10.1039/C5MB00663E
Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. Omi. A J. Integr. Biol. 16, 284–287 (2012).
doi: 10.1089/omi.2011.0118
Heinz, S. et al. Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities. Mol. Cell. 38, 576–589 (2010).
doi: 10.1016/j.molcel.2010.05.004
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–504 (2003).
doi: 10.1101/gr.1239303
Ru, Y. et al. The multiMiR R package and database: integration of microRNA-target interactions along with their disease and drug associations. Nucleic Acids Res. 42, e133–e133 (2014).
doi: 10.1093/nar/gku631
Smilowitz, N. R. et al. Perioperative Major Adverse Cardiovascular and Cerebrovascular Events Associated With Noncardiac Surgery. JAMA Cardiol. 2, 181 (2017).
doi: 10.1001/jamacardio.2016.4792
Kaneko, K. J. & DePamphilis, M. L. TEAD4 establishes the energy homeostasis essential for blastocoel formation. Development. 140, 3680–90 (2013).
doi: 10.1242/dev.093799
Che, P. et al. miR-125a-5p impairs endothelial cell angiogenesis in aging mice via RTEF-1 downregulation. Aging Cell. 13, 926–34 (2014).
doi: 10.1111/acel.12252
Lindenauer, P. K. et al. Perioperative beta-blocker therapy and mortality after major noncardiac surgery. N. Engl. J. Med. 353, 349–61 (2005).
doi: 10.1056/NEJMoa041895
Karuppasamy, P. et al. Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation? Basic Res. Cardiol. 106, 511–9 (2011).
doi: 10.1007/s00395-011-0185-9
Ludman, A. J. et al. Failure to recapture cardioprotection with high-dose atorvastatin in coronary artery bypass surgery: a randomised controlled trial. Basic Res. Cardiol. 106, 1387–95 (2011).
doi: 10.1007/s00395-011-0209-5
Kao, D. P. et al. Therapeutic Molecular Phenotype of β-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy. Circ. Cardiovasc. Genet. 8, 270–83 (2015).
doi: 10.1161/CIRCGENETICS.114.000767
DeGeorge, B. R. & Koch, W. J. Beta blocker specificity: a building block toward personalized medicine. J. Clin. Invest. 117, 86–9 (2007).
doi: 10.1172/JCI30476
Gorre, F. & Vandekerckhove, H. Beta-blockers: focus on mechanism of action. Which beta-blocker, when and why? Acta Cardiol. 65, 565–70 (2010).
pubmed: 21125979
Bertero, E. & Maack, C. Metabolic remodelling in heart failure. Nat. Rev. Cardiol. 15, 457–470 (2018).
doi: 10.1038/s41569-018-0044-6
Lucchinetti, E. et al. Gene regulatory control of myocardial energy metabolism predicts postoperative cardiac function in patients undergoing off-pump coronary artery bypass graft surgery: inhalational versus intravenous anesthetics. Anesthesiology. 106, 444–57 (2007).
doi: 10.1097/00000542-200703000-00008