Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2017

Open Access 01-12-2017 | Research

Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases

Authors: Masood Abu-Halima, Martin Poryo, Nicole Ludwig, Janine Mark, Ina Marsollek, Christian Giebels, Johannes Petersen, Hans-Joachim Schäfers, Ulrich Grundmann, Thomas Pickardt, Andreas Keller, Eckart Meese, Hashim Abdul-Khaliq

Published in: Journal of Translational Medicine | Issue 1/2017

Login to get access

Abstract

Background

Children with congenital heart defects (CHDs) are at high risk for myocardial failure after operative procedures with cardiopulmonary bypass (CPB). Recent studies suggest that microRNAs (miRNA) are involved in the development of CHDs and myocardial failure. Therefore, the aim of this study was to determine alterations in the miRNA profile in heart tissue after cardiac surgery using CPB.

Methods

In total, 14 tissue samples from right atrium were collected from patients before and after connection of the CPB. SurePrint™ 8 × 60K Human v21 miRNA array and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were employed to determine the miRNA expression profile from three patients before and after connection of the CPB. Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools.

Results

According to miRNA array, a total of 90 miRNAs were significantly altered including 29 miRNAs with increased and 61 miRNAs with decreased expression after de-connection of CPB (n = 3) compared to before CPB (n = 3). Seven miRNAs had been validated using RT-qPCR in an independent cohort of 11 patients. Enrichment analyses applying the KEGG database displayed the highest correlation for signaling pathways, cellular community, cardiovascular disease and circulatory system.

Conclusion

Our result identified the overall changes of the miRNome in right atrium tissue of patients with CHDs after CPB. The differentially altered miRNAs lay a good foundation for further understanding of the molecular function of changed miRNAs in regulating CHDs and after CPB in particular.
Appendix
Available only for authorised users
Literature
1.
van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ, Roos-Hesselink JW. Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(21):2241–7.CrossRefPubMed
2.
Schwedler G, Lindinger A, Lange PE, Sax U, Olchvary J, Peters B, Bauer U, Hense HW. Frequency and spectrum of congenital heart defects among live births in Germany: a study of the competence network for congenital heart defects. Clin Res Cardiol. 2011;100(12):1111–7.CrossRefPubMed
3.
Erikssen G, Liestol K, Seem E, Birkeland S, Saatvedt KJ, Hoel TN, Dohlen G, Skulstad H, Svennevig JL, Thaulow E, et al. Achievements in congenital heart defect surgery: a prospective, 40-year study of 7038 patients. Circulation. 2015;131(4):337–46 (discussion 346).CrossRefPubMed
4.
Raissadati A, Nieminen H, Jokinen E, Sairanen H. Progress in late results among pediatric cardiac surgery patients: a population-based 6-decade study with 98% follow-up. Circulation. 2015;131(4):347–53 (discussion 353).CrossRefPubMed
5.
Jones B, Muscara F, Lloyd O, McKinlay L, Justo R. Neurodevelopmental outcome following open heart surgery in infancy: 6-year follow-up. Cardiol Young. 2015;25(5):903–10.CrossRefPubMed
6.
Dollat C, Vergnat M, Laux D, Stos B, Baruteau A, Capderou A, Demontoux S, Hamann M, Mokhfi E, Van Aerschot I, et al. Critical congenital heart diseases in preterm neonates: is early cardiac surgery quite reasonable? Pediatr Cardiol. 2015;36(6):1279–86.CrossRefPubMed
7.
Kumar TK, Charpie JR, Ohye RG, Hirsch-Romano JC, Donohue JE, Yu S, Sood V, Wilkinson DA, Nelson K, Mitchell E, et al. Timing of neonatal cardiac surgery is not associated with perioperative outcomes. J Thorac Cardiovasc Surg. 2014;147(5):1573–9.CrossRefPubMed
8.
Ades AM, Dominguez TE, Nicolson SC, Gaynor JW, Spray TL, Wernovsky G, Tabbutt S. Morbidity and mortality after surgery for congenital cardiac disease in the infant born with low weight. Cardiol Young. 2010;20(1):8–17.CrossRefPubMed
9.
Cheng HH, Wypij D, Laussen PC, Bellinger DC, Stopp CD, Soul JS, Newburger JW, Kussman BD. Cerebral blood flow velocity and neurodevelopmental outcome in infants undergoing surgery for congenital heart disease. Ann Thorac Surg. 2014;98(1):125–32.CrossRefPubMedPubMedCentral
10.
Kang N, Cole T, Tsang V, Elliott M, de Leval M. Risk stratification in paediatric open-heart surgery. Eur J Cardiothorac Surg. 2004;26(1):3–11.CrossRefPubMed
11.
Kussman BD, Wypij D, Laussen PC, Soul JS, Bellinger DC, DiNardo JA, Robertson R, Pigula FA, Jonas RA, Newburger JW. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010;122(3):245–54.CrossRefPubMedPubMedCentral
12.
Wypij D, Newburger JW, Rappaport LA, duPlessis AJ, Jonas RA, Wernovsky G, Lin M, Bellinger DC. The effect of duration of deep hypothermic circulatory arrest in infant heart surgery on late neurodevelopment: the Boston Circulatory Arrest Trial. J Thorac Cardiovasc Surg. 2003;126(5):1397–403.CrossRefPubMed
13.
Creemers EE, Tijsen AJ, Pinto YM. Circulating microRNAs: novel biomarkers and extracellular communicators in cardiovascular disease? Circ Res. 2012;110(3):483–95.CrossRefPubMed
14.
15.
Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet. 2012;13(4):271–82.PubMed
16.
17.
Agarwal U, George A, Bhutani S, Ghosh-Choudhary S, Maxwell JT, Brown ME, Mehta Y, Platt MO, Liang Y, Sahoo S, et al. Experimental, systems, and computational approaches to understanding the microRNA-mediated reparative potential of cardiac progenitor cell-derived exosomes From pediatric patients. Circ Res. 2017;120(4):701–12.CrossRefPubMed
18.
van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS, Hill JA, Olson EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci USA. 2008;105(35):13027–32.CrossRefPubMedPubMedCentral
19.
Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature. 2008;456(7224):980–4.CrossRefPubMed
20.
Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J. 2010;31(6):659–66.CrossRefPubMed
21.
Calafiore AM, Teodori G, Mezzetti A, Bosco G, Verna AM, Di Giammarco G, Lapenna D. Intermittent antegrade warm blood cardioplegia. Ann Thorac Surg. 1995;59(2):398–402.CrossRefPubMed
22.
Abu-Halima M, Ludwig N, Hart M, Leidinger P, Backes C, Keller A, Hammadeh M, Meese E. Altered micro-ribonucleic acid expression profiles of extracellular microvesicles in the seminal plasma of patients with oligoasthenozoospermia. Fertil Steril. 2016;106:1061–9.CrossRefPubMed
23.
Vlachos IS, Zagganas K, Paraskevopoulou MD, Georgakilas G, Karagkouni D, Vergoulis T, Dalamagas T, Hatzigeorgiou AG. DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res. 2015;43(W1):W460–6.CrossRefPubMedPubMedCentral
24.
Hamberg M, Backes C, Fehlmann T, Hart M, Meder B, Meese E, Keller A. MiRTargetLink–miRNAs, genes and interaction networks. Int J Mol Sci. 2016;17(4):564.CrossRefPubMedPubMedCentral
25.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–8.CrossRefPubMed
26.
Contu R, Latronico MV, Condorelli G. Circulating microRNAs as potential biomarkers of coronary artery disease: a promise to be fulfilled? Circ Res. 2010;107(5):573–4.CrossRefPubMed
27.
Dickinson BA, Semus HM, Montgomery RL, Stack C, Latimer PA, Lewton SM, Lynch JM, Hullinger TG, Seto AG, van Rooij E. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure. Eur J Heart Fail. 2013;15(6):650–9.CrossRefPubMed
28.
Endo K, Naito Y, Ji X, Nakanishi M, Noguchi T, Goto Y, Nonogi H, Ma X, Weng H, Hirokawa G, et al. MicroRNA 210 as a biomarker for congestive heart failure. Biol Pharm Bull. 2013;36(1):48–54.CrossRefPubMed
29.
Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail. 2012;14(2):147–54.CrossRefPubMed
30.
Latronico MV, Catalucci D, Condorelli G. MicroRNA and cardiac pathologies. Physiol Genom. 2008;34(3):239–42.CrossRef
31.
Tijsen AJ, Creemers EE, Moerland PD, de Windt LJ, van der Wal AC, Kok WE, Pinto YM. MiR423-5p as a circulating biomarker for heart failure. Circ Res. 2010;106(6):1035–9.CrossRefPubMed
32.
Wang K, Liu F, Zhou LY, Ding SL, Long B, Liu CY, Sun T, Fan YY, Sun L, Li PF. miR-874 regulates myocardial necrosis by targeting caspase-8. Cell Death Dis. 2013;4:e709.CrossRefPubMedPubMedCentral
33.
Li C, Li X, Gao X, Zhang R, Zhang Y, Liang H, Xu C, Du W, Zhang Y, Liu X, et al. MicroRNA-328 as a regulator of cardiac hypertrophy. Int J Cardiol. 2014;173(2):268–76.CrossRefPubMed
34.
van Rooij E, Quiat D, Johnson BA, Sutherland LB, Qi X, Richardson JA, Kelm RJ Jr, Olson EN. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev Cell. 2009;17(5):662–73.CrossRefPubMedPubMedCentral
35.
36.
Callis TE, Pandya K, Seok HY, Tang RH, Tatsuguchi M, Huang ZP, Chen JF, Deng Z, Gunn B, Shumate J, et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Investig. 2009;119(9):2772–86.CrossRefPubMedPubMedCentral
37.
Tony H, Meng K, Wu B, Yu A, Zeng Q, Yu K, Zhong Y. MicroRNA-208a dysregulates apoptosis genes expression and promotes cardiomyocyte apoptosis during ischemia and its silencing improves cardiac function after myocardial infarction. Med Inflamm. 2015;2015:479123.CrossRef
38.
Winbanks CE, Ooi JY, Nguyen SS, McMullen JR, Bernardo BC. MicroRNAs differentially regulated in cardiac and skeletal muscle in health and disease: potential drug targets? Clin Exp Pharmacol Physiol. 2014;41(9):727–37.PubMed
39.
Deacon DC, Nevis KR, Cashman TJ, Zhou Y, Zhao L, Washko D, Guner-Ataman B, Burns CG, Burns CE. The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development. 2010;137(11):1887–96.CrossRefPubMed
40.
Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D. miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature. 2009;460(7256):705–10.PubMedPubMedCentral
41.
Thum T, Galuppo P, Wolf C, Fiedler J, Kneitz S, van Laake LW, Doevendans PA, Mummery CL, Borlak J, Haverich A, et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation. 2007;116(3):258–67.CrossRefPubMed
42.
Yu Z, Raabe T, Hecht NB. MicroRNA Mirn122a reduces expression of the posttranscriptionally regulated germ cell transition protein 2 (Tnp2) messenger RNA (mRNA) by mRNA cleavage. Biol Reprod. 2005;73(3):427–33.CrossRefPubMed
43.
Liu H, Qin H, Chen GX, Liang MY, Rong J, Yao JP, Wu ZK. Comparative expression profiles of microRNA in left and right atrial appendages from patients with rheumatic mitral valve disease exhibiting sinus rhythm or atrial fibrillation. J Transl Med. 2014;12:90.CrossRefPubMedPubMedCentral
44.
Liu X, Cheng Y, Zhang S, Lin Y, Yang J, Zhang C. A necessary role of miR-221 and miR-222 in vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 2009;104(4):476–87.CrossRefPubMedPubMedCentral
45.
Liu X, Xiao J, Zhu H, Wei X, Platt C, Damilano F, Xiao C, Bezzerides V, Bostrom P, Che L, et al. miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell Metab. 2015;21(4):584–95.CrossRefPubMedPubMedCentral
46.
Zhang J, Chang JJ, Xu F, Ma XJ, Wu Y, Li WC, Wang HJ, Huang GY, Ma D. MicroRNA deregulation in right ventricular outflow tract myocardium in nonsyndromic tetralogy of fallot. Can J Cardiol. 2013;29(12):1695–703.CrossRefPubMed
47.
Ucar A, Gupta SK, Fiedler J, Erikci E, Kardasinski M, Batkai S, Dangwal S, Kumarswamy R, Bang C, Holzmann A, et al. The miRNA-212/132 family regulates both cardiac hypertrophy and cardiomyocyte autophagy. Nat Commun. 1078;2012:3.
48.
Zhou L, Zang G, Zhang G, Wang H, Zhang X, Johnston N, Min W, Luke P, Jevnikar A, Haig A, et al. MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation. PLoS ONE. 2013;8(11):e79805.CrossRefPubMedPubMedCentral
49.
Fan KL, Zhang HF, Shen J, Zhang Q, Li XL. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J. 2013;65(1):12–6.CrossRefPubMedPubMedCentral
50.
Slagsvold KH, Johnsen AB, Rognmo O, Hoydal M, Wisloff U, Wahba A. Comparison of left versus right atrial myocardium in patients with sinus rhythm or atrial fibrillation-an assessment of mitochondrial function and microRNA expression. Physiol Rep. 2014;2(8):e12124.CrossRefPubMedPubMedCentral
51.
Hazarika S, Farber CR, Dokun AO, Pitsillides AN, Wang T, Lye RJ, Annex BH. MicroRNA-93 controls perfusion recovery after hindlimb ischemia by modulating expression of multiple genes in the cell cycle pathway. Circulation. 2013;127(17):1818–28.CrossRefPubMed
52.
McManus DD, Lin H, Tanriverdi K, Quercio M, Yin X, Larson MG, Ellinor PT, Levy D, Freedman JE, Benjamin EJ. Relations between circulating microRNAs and atrial fibrillation: data from the Framingham Offspring Study. Heart Rhythm. 2014;11(4):663–9.CrossRefPubMedPubMedCentral
53.
Chen F, Zhao X, Peng J, Bo L, Fan B, Ma D. Integrated microRNA-mRNA analysis of coronary artery disease. Mol Biol Rep. 2014;41(8):5505–11.CrossRefPubMed
54.
Saddic LA, Chang TW, Sigurdsson MI, Heydarpour M, Raby BA, Shernan SK, Aranki SF, Body SC, Muehlschlegel JD. Integrated microRNA and mRNA responses to acute human left ventricular ischemia. Physiol Genom. 2015;47(10):455–62.CrossRef
55.
Cakmak HA, Coskunpinar E, Ikitimur B, Barman HA, Karadag B, Tiryakioglu NO, Kahraman K, Vural VA. The prognostic value of circulating microRNAs in heart failure: preliminary results from a genome-wide expression study. J Cardiovasc Med. 2015;16(6):431–7.CrossRef
56.
Huang X, Zuo J. Emerging roles of miR-210 and other non-coding RNAs in the hypoxic response. Acta Biochim Biophys Sin. 2014;46(3):220–32.CrossRefPubMed
57.
Wong LL, Armugam A, Sepramaniam S, Karolina DS, Lim KY, Lim JY, Chong JP, Ng JY, Chen YT, Chan MM, et al. Circulating microRNAs in heart failure with reduced and preserved left ventricular ejection fraction. Eur J Heart Fail. 2015;17(4):393–404.CrossRefPubMed
58.
Bruneau BG. Signaling and transcriptional networks in heart development and regeneration. Cold Spring Harbor Perspect Biol. 2013;5(3):a008292.CrossRef
59.
Galasso G, De Rosa R, Piscione F, Iaccarino G, Vosa C, Sorriento D, Piccolo R, Rapacciuolo A, Walsh K, Chiariello M. Myocardial expression of FOXO3a-Atrogin-1 pathway in human heart failure. Eur J Heart Fail. 2010;12(12):1290–6.CrossRefPubMed
60.
Holweg CT, Baan CC, Niesters HG, Vantrimpont PJ, Mulder PG, Maat AP, Weimar W, Balk AH. TGF-beta1 gene polymorphisms in patients with end-stage heart failure. J Heart Lung Transpl. 2001;20(9):979–84.CrossRef
61.
62.
Xin M, Kim Y, Sutherland LB, Murakami M, Qi X, McAnally J, Porrello ER, Mahmoud AI, Tan W, Shelton JM, et al. Hippo pathway effector Yap promotes cardiac regeneration. Proc Natl Acad Sci USA. 2013;110(34):13839–44.CrossRefPubMedPubMedCentral
63.
Communal C, Colucci WS. The control of cardiomyocyte apoptosis via the beta-adrenergic signaling pathways. Arch Mal Coeur Vaiss. 2005;98(3):236–41.PubMed
64.
Heallen T, Zhang M, Wang J, Bonilla-Claudio M, Klysik E, Johnson RL, Martin JF. Hippo pathway inhibits Wnt signaling to restrain cardiomyocyte proliferation and heart size. Science. 2011;332(6028):458–61.CrossRefPubMedPubMedCentral
65.
Xin M, Kim Y, Sutherland LB, Qi X, McAnally J, Schwartz RJ, Richardson JA, Bassel-Duby R, Olson EN. Regulation of insulin-like growth factor signaling by Yap governs cardiomyocyte proliferation and embryonic heart size. Sci Signal. 2011;4(196):ra70.CrossRefPubMedPubMedCentral
66.
67.
Fritz G, Kaina B. Stress factors affecting expression of O6-methylguanine-DNA methyltransferase mRNA in rat hepatoma cells. Biochem Biophys Acta. 1992;1171(1):35–40.PubMed
68.
Siwik DA, Tzortzis JD, Pimental DR, Chang DL, Pagano PJ, Singh K, Sawyer DB, Colucci WS. Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res. 1999;85(2):147–53.CrossRefPubMed
69.
Chen J, Huang ZP, Seok HY, Ding J, Kataoka M, Zhang Z, Hu X, Wang G, Lin Z, Wang S, et al. mir-17-92 cluster is required for and sufficient to induce cardiomyocyte proliferation in postnatal and adult hearts. Circ Res. 2013;112(12):1557–66.CrossRefPubMedPubMedCentral
70.
Hassink RJ, Pasumarthi KB, Nakajima H, Rubart M, Soonpaa MH, de la Riviere AB, Doevendans PA, Field LJ. Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction. Cardiovasc Res. 2008;78(1):18–25.CrossRefPubMed
71.
Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, et al. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature. 2011;480(7377):372–5.CrossRefPubMedPubMedCentral
72.
Jackson T, Allard MF, Sreenan CM, Doss LK, Bishop SP, Swain JL. The c-myc proto-oncogene regulates cardiac development in transgenic mice. Mol Cell Biol. 1990;10(7):3709–16.CrossRefPubMedPubMedCentral
Metadata
Title
Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases
Authors
Masood Abu-Halima
Martin Poryo
Nicole Ludwig
Janine Mark
Ina Marsollek
Christian Giebels
Johannes Petersen
Hans-Joachim Schäfers
Ulrich Grundmann
Thomas Pickardt
Andreas Keller
Eckart Meese
Hashim Abdul-Khaliq
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2017
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-017-1213-9

Other articles of this Issue 1/2017

Journal of Translational Medicine 1/2017 Go to the issue

Review

p53: key conductor of all anti-acne therapies

Protocol

Effect of a 6-month pedometer-based walking intervention on functional capacity in patients with chronic heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction: study protocol for two multicenter randomized controlled trials

Research

The effect of renal denervation in an experimental model of chronic renal insufficiency, The REmnant kidney Denervation In Pigs study (REDIP study)

Research

Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma

Research

Prediction of anti-inflammatory proteins/peptides: an insilico approach

Review

The pathophysiological role of mitochondrial oxidative stress in lung diseases
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits