Silencing miR-370-3p rescues funny current and sinus node function in heart failure.
Animals
Binding Sites
Body Weight
Cardiomegaly
Computational Biology
Down-Regulation
Fibrosis
Gene Silencing
Heart Failure
/ genetics
Heart Rate
Humans
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
/ genetics
Male
Mice
Mice, Inbred C57BL
MicroRNAs
/ genetics
Rats
Sinoatrial Node
/ physiopathology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
09 07 2020
09 07 2020
Historique:
received:
12
06
2019
accepted:
02
06
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
26
1
2021
Statut:
epublish
Résumé
Bradyarrhythmias are an important cause of mortality in heart failure and previous studies indicate a mechanistic role for electrical remodelling of the key pacemaking ion channel HCN4 in this process. Here we show that, in a mouse model of heart failure in which there is sinus bradycardia, there is upregulation of a microRNA (miR-370-3p), downregulation of the pacemaker ion channel, HCN4, and downregulation of the corresponding ionic current, I
Identifiants
pubmed: 32647133
doi: 10.1038/s41598-020-67790-0
pii: 10.1038/s41598-020-67790-0
pmc: PMC7347645
doi:
Substances chimiques
Hcn4 protein, mouse
0
Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
0
MIRN370 microRNA, human
0
MIRN370 microRNA, mouse
0
MIRN370 microRNA, rat
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11279Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL113084
Pays : United States
Organisme : NIH HHS
ID : HL135109
Pays : United States
Organisme : NIH HHS
ID : HL115580
Pays : United States
Organisme : British Heart Foundation
ID : PG/17/32/32987
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P015816/1
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL115580
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135109
Pays : United States
Organisme : British Heart Foundation
ID : FS/19/1/34035
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/18/2/33392
Pays : United Kingdom
Références
Ambrosy, A. P. et al. The global health and economic burden of hospitalizations for heart failure: lessons learned from hospitalized heart failure registries. J. Am. Coll. Cardiol. 63, 1123–1133 (2014).
pubmed: 24491689
Benes, J. et al. Resting heart rate and heart rate reserve in advanced heart failure have distinct pathophysiologic correlates and prognostic impact: a prospective pilot study. J. Am. Coll. Cardiol. Heart Fail. 1, 259–266 (2013).
Crespo-Leiro, M. G. et al. European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions. Eur. J. Heart Fail. 18, 613–625 (2016).
pubmed: 27324686
Fox, K. et al. Resting heart rate in cardiovascular disease. J. Am. Coll. Cardiol. 50, 823–830 (2007).
pubmed: 17719466
Swedberg, K. et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 376, 875–885 (2010).
pubmed: 20801500
Gang, U. J. et al. Heart rhythm at the time of death documented by an implantable loop recorder. Europace 12, 254–260 (2010).
pubmed: 20019013
Faggiano, P., d’Aloia, A., Gualeni, A., Gardini, A. & Giordano, A. Mechanisms and immediate outcome of in-hospital cardiac arrest in patients with advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am. J. Cardiol. 87, 651–655 (2001).
Stevenson, W. G., Stevenson, L. W., Middlekauff, H. R. & Saxon, L. A. Sudden death prevention in patients with advanced ventricular dysfunction. Circulation 88, 2953–2961 (1993).
pubmed: 8252708
Jose, A. D. & Taylor, R. R. Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. J. Clin. Investig. 48, 2019–2031 (1969).
pubmed: 5398888
Yanni, J. et al. Changes in ion channel gene expression underlying heart failure-induced sinoatrial node dysfunction. Circ. Heart Fail. 4, 496–508 (2011).
pubmed: 21565973
Zicha, S., Fernandez-Velasco, M., Lonardo, G., L’Heureux, N. & Nattel, S. Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model. Cardiovasc. Res. 66, 472–481 (2005).
pubmed: 15914112
Opthof, T. et al. Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death. Circulation 101, 2975–2980 (2000).
pubmed: 10869272
Sanders, P., Kistler, P. M., Morton, J. B., Spence, S. J. & Kalman, J. M. Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve. Circulation 110, 897–903 (2004).
pubmed: 15302799
Swaminathan, P. D. et al. Oxidized CaMKII causes cardiac sinus node dysfunction in mice. J. Clin. Investig. 121, 3277–3288 (2011).
pubmed: 21785215
Verkerk, A. O., Wilders, R., Coronel, R., Ravesloot, J. H. & Verheijck, E. E. Ionic remodeling of sinoatrial node cells by heart failure. Circulation 108, 760–766 (2003).
pubmed: 12885752
Li, N. et al. Redundant and diverse intranodal pacemakers and conduction pathways protect the human sinoatrial node from failure. Sci. Transl. Med. 9, eaam5607 (2017).
pubmed: 28747516
pmcid: 5775890
Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nat. Rev. Genet. 10, 94–108 (2009).
pubmed: 19148191
pmcid: 2724769
Filipowicz, W., Bhattacharyya, S. N. & Sonenberg, N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?. Nat. Rev. Genet. 9, 102–114 (2008).
pubmed: 18197166
Kozomara, A. & Griffiths-Jones, S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42, D68-73 (2014).
pubmed: 24275495
Gaken, J. et al. A functional assay for microRNA target identification and validation. Nucleic Acids Res. 40, e75 (2012).
pubmed: 22323518
pmcid: 3378903
Yang, B. et al. The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat. Med. 13, 486–491 (2007).
pubmed: 17401374
Thum, T., Catalucci, D. & Bauersachs, J. MicroRNAs: novel regulators in cardiac development and disease. Cardiovasc. Res. 79, 562–570 (2008).
pubmed: 18511432
Farh, K. K. et al. The widespread impact of mammalian microRNAs on mRNA repression and evolution. Science 310, 1817–1821 (2005).
pubmed: 16308420
Hoekstra, M. et al. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochem. Biophys. Res. Commun. 394, 792–797 (2010).
pubmed: 20230787
Bronze-da-Rocha, E. MicroRNAs expression profiles in cardiovascular diseases. BioMed. Res. Int. 2014, 985408 (2014).
pubmed: 25013816
pmcid: 4075084
Motawae, T. M., Ismail, M. F., Shabayek, M. I. & Seleem, M. M. MicroRNAs 9 and 370 association with biochemical markers in T2D and CAD complication of T2D. PLoS ONE 10, e0126957 (2015).
pubmed: 25978320
pmcid: 4433316
Patten, R. D. & Hall-Porter, M. R. Small animal models of heart failure: development of novel therapies, past and present. Circ. Heart Fail. 2, 138–144 (2009).
pubmed: 19808329
Gao, S., Ho, D., Vatner, D. E. & Vatner, S. F. Echocardiography in mice. Curr. Protoc. Mouse Biol. 1, 71–83 (2011).
pubmed: 21743841
pmcid: 3130310
Dobrzynski, H. et al. Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues. Pharmacol. Ther. 139, 260–288 (2013).
pubmed: 23612425
Nattel, S., Maguy, A., Le Bouter, S. & Yeh, Y. H. Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol. Rev. 87, 425–456 (2007).
pubmed: 17429037
Skovsted, P. & Sapthavichaikul, S. The effects of isoflurane on arterial pressure, pulse rate, autonomic nervous activity, and barostatic reflexes. Can. Anaesth. Soc. J. 24, 304–314 (1977).
pubmed: 871935
Huneke, R., Faßl, J., Rossaint, R. & Luckhoff, A. Effects of volatile anesthetics on cardiac ion channels. Acta Anaesthesiol. Scand. 48, 547–561 (2004).
pubmed: 15101848
Lakatta, E. G., Maltsev, V. A. & Vinogradova, T. M. A coupled SYSTEM of intracellular Ca
pubmed: 20203315
pmcid: 2837285
Verkerk, A. O., van Borren, M. M., van Ginneken, A. C. & Wilders, R. Ca
pubmed: 25698973
pmcid: 4313601
Tellez, J. O. et al. Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit. Circ. Res. 99, 1384–1393 (2006).
pubmed: 17082478
Linscheid, N. et al. Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nat. Commun. 10, 2889 (2019).
pubmed: 31253831
pmcid: 6599035
DiFrancesco, D. The role of the funny current in pacemaker activity. Circ. Res. 106, 434–446 (2010).
pubmed: 20167941
Herrmann, S., Layh, B. & Ludwig, A. Novel insights into the distribution of cardiac HCN channels: an expression study in the mouse heart. J. Mol. Cell. Cardiol. 51, 997–1006 (2011).
pubmed: 21945247
Kuratomi, S. et al. The cardiac pacemaker-specific channel Hcn4 is a direct transcriptional target of MEF2. Cardiovasc. Res. 83, 682–687 (2009).
pubmed: 19477969
Liang, X. et al. Transcription factor ISL1 is essential for pacemaker development and function. J. Clin. Investig. 125, 3256–3268 (2015).
pubmed: 26193633
Vedantham, V., Galang, G., Evangelista, M., Deo, R. C. & Srivastava, D. RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells. Circ. Res. 116, 797–803 (2015).
pubmed: 25623957
pmcid: 4344860
Espinoza-Lewis, R. A. et al. Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice. Dev. Biol. 356, 359–369 (2011).
pubmed: 21640717
pmcid: 3143305
Kuratomi, S. et al. NRSF regulates the developmental and hypertrophic changes of HCN4 transcription in rat cardiac myocytes. Biochem. Biophys. Res. Commun. 353, 67–73 (2007).
pubmed: 17173866
Hoogaars, W. M. et al. Tbx3 controls the sinoatrial node gene program and imposes pacemaker function on the atria. Genes Dev. 21, 1098–1112 (2007).
pubmed: 17473172
pmcid: 1855235
Kapoor, N., Liang, W., Marban, E. & Cho, H. C. Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nat. Biotechnol. 31, 54–62 (2013).
pubmed: 23242162
van Eif, V. W. W. et al. Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program. Development 146, dev173161 (2019).
pubmed: 30936179
Bang, C. et al. Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J. Clin. Investig. 124, 2136–2146 (2014).
pubmed: 24743145
Baskerville, S. & Bartel, D. P. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11, 241–247 (2005).
pubmed: 15701730
pmcid: 1370713
Kim, Y. K. & Kim, V. N. Processing of intronic microRNAs. EMBO J. 26, 775–783 (2007).
pubmed: 17255951
pmcid: 1794378
Mehel, H. et al. Phosphodiesterase-2 is up-regulated in human failing hearts and blunts beta-adrenergic responses in cardiomyocytes. J. Am. Coll. Cardiol. 62, 1596–1606 (2013).
pubmed: 23810893
Feng, H. J. et al. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy. Braz. J. Med. Biol. Res. 47, 361–368 (2014).
pubmed: 24728214
pmcid: 4075303
Cheng, Y. et al. MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy?. Am. J. Pathol. 170, 1831–1840 (2007).
pubmed: 17525252
pmcid: 1899438
Fang, Z. & Rajewsky, N. The impact of miRNA target sites in coding sequences and in 3′UTRs. PLoS ONE 6, e18067 (2011).
pubmed: 21445367
pmcid: 3062573
D’Souza, A. et al. Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat. Commun. 5, 3775 (2014).
pubmed: 24825544
pmcid: 4024745
Baek, D. et al. The impact of microRNAs on protein output. Nature 455, 64–71 (2008).
pubmed: 18668037
pmcid: 2745094
Krutzfeldt, J. et al. Silencing of microRNAs in vivo with “antagomirs”. Nature 438, 685–689 (2005).
pubmed: 16258535
Czech, M. P. MicroRNAs as therapeutic targets. N. Engl. J. Med. 354, 1194–1195 (2006).
pubmed: 16540623
Bloch Thomsen, P. E. et al. Long-term recording of cardiac arrhythmias with an implantable cardiac monitor in patients with reduced ejection fraction after acute myocardial infarction: the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) study. Circulation 122, 1258–1264 (2010).
pubmed: 20837897
Nikolaidou, T., Ghosh, J. M. & Clark, A. L. Outcomes related to first-degree atrioventricular block and therapeutic implications in patients with heart failure. J. Am. Coll. Cardiol. Clin. Electrophysiol. 2, 181–192 (2016).
Padeletti, L. et al. Concordant versus discordant left bundle branch block in heart failure patients: novel clinical value of an old electrocardiographic diagnosis. J. Card. Fail. 16, 320–326 (2010).
pubmed: 20350699
Shinohara, T. et al. Ca
pubmed: 20889842
pmcid: 3006277
Glukhov, A. V. et al. Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1. Eur. Heart J. 36, 686–697 (2015).
pubmed: 24216388
Farin, H. F. et al. Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors. J. Biol. Chem. 282, 25748–25759 (2007).
pubmed: 17584735
Yuan, H. & Gao, J. The role of miR-370 in fibrosis after myocardial infarction. Molecular Medicine Reports 15, 3041–3047 (2017).
pubmed: 28350072
pmcid: 5428907
Lu, C. H. et al. MicroRNA-370 attenuates hepatic fibrogenesis by targeting smoothened. Dig. Dis. Sci. 60, 2038–2048 (2015).
pubmed: 25686745
Bang, C. et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J. Clin. Investig. 124, 2136–2146 (2014).
pubmed: 24743145
Iliopoulos, D., Drosatos, K., Hiyama, Y., Goldberg, I. J. & Zannis, V. I. MicroRNA-370 controls the expression of microRNA-122 and Cpt1alpha and affects lipid metabolism. J. Lipid Res. 51, 1513–1523 (2010).
pubmed: 20124555
pmcid: 3035515
Florea, V. G. & Cohn, J. N. The autonomic nervous system and heart failure. Circ. Res. 114, 1815–1826 (2014).
pubmed: 24855204
Brubaker, P. H. & Kitzman, D. W. Chronotropic incompetence: causes, consequences, and management. Circulation 123, 1010–1020 (2011).
pubmed: 21382903
pmcid: 3065291
Roche, F. et al. Chronotropic incompetence response to exercise in congestive heart failure, relationship with the cardiac autonomic status. Clin. Physiol. 21, 335–342 (2001).
pubmed: 11380533
Bristow, M. R. et al. Beta-adrenergic pathways in nonfailing and failing human ventricular myocardium. Circulation 82, I12-25 (1990).
pubmed: 2164894
Colucci, W. S. et al. Impaired chronotropic response to exercise in patients with congestive heart failure. Role of postsynaptic beta-adrenergic desensitization. Circulation 80, 314–323 (1989).
pubmed: 2546698
Samejima, H. et al. Relationship between impaired chronotropic response, cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. Jpn. Heart J. 44, 515–525 (2003).
pubmed: 12906033
Du, Y. et al. β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats. J. Physiol. Biochem. 72, 293–302 (2016).
pubmed: 26995749
Alboni, P. et al. Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial. Circulation 96, 260–266 (1997).
pubmed: 9236443
Alboni, P., Scarfo, S. & Fuca, G. Development of heart failure in bradycardic sick sinus syndrome. Ital. Heart J. 2, 9–12 (2001).
pubmed: 11214707
Iwataki, M. et al. Different characteristics of heart failure due to pump failure and bradyarrhythmia. J. Echocardiogr. 13, 27–34 (2015).
pubmed: 25750577
Levine, S. A., Miller, H. & Penton, G. B. Some clinical features of complete heart block. Circulation 13, 801–824 (1956).
pubmed: 13356435
Opasich, C. et al. Concomitant factors of decompensation in chronic heart failure. Am. J. Cardiol. 78, 354–357 (1996).
pubmed: 8759821
Alboni, P., Brignole, M., Menozzi, C. & Scarfo, S. Is sinus bradycardia a factor facilitating overt heart failure?. Eur. J. Heart Fail. 20, 252–255 (1999).
Caliskan, K., Balk, A. H., Jordaens, L. & Szili-Torok, T. Bradycardiomyopathy: the case for a causative relationship between severe sinus bradycardia and heart failure. J. Cardiovasc. Electrophysiol. 21, 822–824 (2010).
pubmed: 20132390
Ntalianis, A. & Nanas, J. N. Immediate relief of congestive heart failure by ventricular pacing in chronic bradycardia. Cardiol. Rev. 14, e14-15 (2006).
pubmed: 16924158
Alboni, P., Scarfo, S. & Fuca, G. Development of heart failure in bradycardic sick sinus syndrome. Ital. Heart J. 2, 9–12 (2001).
pubmed: 11214707
Tsuji, Y. et al. Ionic mechanisms of acquired QT prolongation and torsades de pointes in rabbits with chronic complete atrioventricular block. Circulation 106, 2012–2018 (2002).
pubmed: 12370228
Hu, Y., Gurev, V., Constantino, J. & Trayanova, N. Efficient preloading of the ventricles by a properly timed atrial contraction underlies stroke work improvement in the acute response to cardiac resynchronization therapy. Heart Rhythm 10, 1800–1806 (2013).
pubmed: 23928177
Panidis, I. P., Ross, J., Munley, B., Nestico, P. & Mintz, G. S. Diastolic mitral regurgitation in patients with atrioventricular conduction abnormalities: a common finding by Doppler echocardiography. J. Am. Coll. Cardiol. 7, 768–774 (1986).
pubmed: 3958334
Liu, W. et al. A novel immunomodulator, FTY-720 reverses existing cardiac hypertrophy and fibrosis from pressure overload by targeting NFAT (nuclear factor of activated T-cells) signaling and periostin. Circ. Heart Fail. 6, 833–844 (2013).
pubmed: 23753531
Boon, R. A. et al. MicroRNA-34a regulates cardiac ageing and function. Nature 495, 107–110 (2013).
pubmed: 23426265
Wahlquist, C. et al. Inhibition of miR-25 improves cardiac contractility in the failing heart. Nature 508, 531–535 (2014).
pubmed: 24670661
pmcid: 4131725
Stypmann, J. et al. Echocardiographic assessment of global left ventricular function in mice. Lab. Anim. 43, 127–137 (2009).
pubmed: 19237453
Yamamoto, M., Honjo, H., Niwa, R. & Kodama, I. Low frequency extracellular potentials recorded from the sinoatrial node. Cardiovasc. Res. 39, 360–372 (1998).
pubmed: 9798521
Dobrzynski, H. Immunocytochemical localisation of K
Marger, L. et al. Pacemaker activity and ionic currents in mouse atrioventricular node cells. Channels (Austin) 5, 241–250 (2011).
Morris, G. et al. Characterisation of right atrial pacemaker tissue and its utility for biopacemaking in sick sinus syndrome. Cardiovasc. Res. 100, 160–169 (2013).
pubmed: 23787003
Vergoulis, T. et al. TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support. Nucleic Acids Res. 40, D222–D229 (2012).
pubmed: 22135297
Naeem, A. et al. Bioinformatics analysis of microRNA and putative target genes in bovine mammary tissue infected with Streptococcus uberis. J. Dairy Sci. 95, 6397–6408 (2012).
pubmed: 22959936
Moro, A. et al. MicroRNA-dependent regulation of biomechanical genes establishes tissue stiffness homeostasis. Nat. Cell Biol. 21, 348–358 (2019).
pubmed: 30742093
pmcid: 6528464
Li, N. et al. Molecular mapping of sinoatrial node HCN channel expression in the human heart. Circ. Arrhythm. Electrophysiol. 8, 1219–1227 (2015).
pubmed: 26304511
pmcid: 4618238
Chandler, N. J. et al. Molecular architecture of the human sinus node—insights into the function of the cardiac pacemaker. Circulation 119, 1562–1575 (2009).
pubmed: 19289639