Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Das Thema chronische Unterbauch- und Viszeralschmerzen wird im Live-Webinar am 7. Mai von 17.30 bis 19 Uhr aus internistischer, gynäkologischer und psychologisch-neurowissenschaftlicher Perspektive beleuchtet. Besprochen werden krankheitsbedingte Ursachen, Mechanismen der kognitiven Schmerzmodulation sowie mögliche Therapieoptionen. Die Fortbildung ist mit 2 CME-Punkten zertifiziert. Melden Sie sich jetzt an!
Erweiterte Suche
Anmelden
nach oben
Current Cardiology Reports
Erschienen in: Current Cardiology Reports 8/2021

01.08.2021 | Regenerative Medicine (SM Wu, Section Editor)

Molecular Profiling of the Cardiac Conduction System: the Dawn of a New Era

verfasst von: Sruthi Mantri, Sean M. Wu, William R. Goodyer

Erschienen in: Current Cardiology Reports | Ausgabe 8/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

Recent technological advances have led to an increased ability to define the gene expression profile of the cardiac conduction system (CCS). Here, we review the most salient studies to emerge in recent years and discuss existing gaps in our knowledge as well as future areas of investigation.

Recent Findings

Molecular profiling of the CCS spans several decades. However, the advent of high-throughput sequencing strategies has allowed for the discovery of unique transcriptional programs of the many diverse CCS cell types.

Summary

The CCS, a diverse structure with significant inter- and intra-component cellular heterogeneity, is essential to the normal function of the heart. Progress in transcriptomic profiling has improved the resolution and depth of characterization of these unique and clinically relevant CCS cell types. Future studies leveraging this big data will play a crucial role in improving our understanding of CCS development and function as well as translating these findings into tangible translational tools for the improved detection, prevention, and treatment of cardiac arrhythmias.
Literatur
1.
2.
Padala SK, Cabrera J-A, Ellenbogen KA. Anatomy of the cardiac conduction system. Pacing Clin Electrophysiol PACE. 2021;44(1):15–25.PubMedCrossRef
3.
van Eif VWW, Devalla HD, Boink GJJ, Christoffels VM. Transcriptional regulation of the cardiac conduction system. Nat Rev Cardiol. 2018;15(10):617–30.PubMedCrossRef
4.
5.
• Goodyer WR, Beyersdorf BM, Paik DT, Tian L, Li G, Buikema JW, et al. Transcriptomic profiling of the developing cardiac conduction system at single-cell resolution. Circ Res. 2019;125(4):379–97 This study represents the first effort to successfully define the transcriptional profile of the entire murine CCS at single-cell resolution.PubMedPubMedCentralCrossRef
6.
Cabrera J-Á, Anderson RH, Macías Y, Nevado-Medina J, Porta-Sánchez A, Rubio JM, et al. Variable arrangement of the atrioventricular conduction axis within the triangle of Koch: implications for permanent His bundle pacing. JACC Clin Electrophysiol. 2020;6(4):362–77.PubMedCrossRef
7.
Billette J, Tadros R. An integrated overview of AV node physiology. Pacing Clin Electrophysiol. 2019;42(7):805–20.PubMedCrossRef
8.
van Weerd JH, Christoffels VM. The formation and function of the cardiac conduction system. Development. 2016;143(2):197–210.PubMedCrossRef
9.
Aanhaanen WTJ, Mommersteeg MTM, Norden J, Wakker V, de Gier-de Vries C, Anderson RH, et al. Developmental origin, growth, and three-dimensional architecture of the atrioventricular conduction axis of the mouse heart. Circ Res. 2010;107(6):728–36.PubMedCrossRef
10.
Chandler NJ, Greener ID, Tellez JO, Inada S, Musa H, Molenaar P, et al. Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker. Circulation. 2009;119(12):1562–75.PubMedCrossRef
11.
Csepe TA, Zhao J, Hansen BJ, Li N, Sul LV, Lim P, et al. Human sinoatrial node structure: 3D microanatomy of sinoatrial conduction pathways. Prog Biophys Mol Biol. 2016;120(1–3):164–78.PubMedCrossRef
12.
Tranum-Jensen J, Wilde AA, Vermeulen JT, Janse MJ. Morphology of electrophysiologically identified junctions between Purkinje fibers and ventricular muscle in rabbit and pig hearts. Circ Res. 1991 Aug;69(2):429–37.PubMedCrossRef
13.
Martinez-Palomo A, Alanis J, Benitez D. Transitional cardiac cells of the conductive system of the dog heart. Distinguishing morphological and electrophysiological features. J Cell Biol. 1970;47(1):1–17.PubMedPubMedCentralCrossRef
14.
Vigmond EJ, Stuyvers BD. Modeling our understanding of the His-Purkinje system. Prog Biophys Mol Biol. 2016;120(1–3):179–88.PubMedCrossRef
15.
Haissaguerre M, Vigmond E, Stuyvers B, Hocini M, Bernus O. Ventricular arrhythmias and the His-Purkinje system. Nat Rev Cardiol. 2016;13(3):155–66.PubMedCrossRef
16.
Keith A, Flack MW. The auriculo-ventricular bundle of the human heart. 1906. Ann Noninvasive Electrocardiol Off J Int Soc Holter Noninvasive Electrocardiol Inc. 2004;9(4):400–9.CrossRef
17.
Monfredi O, Dobrzynski H, Mondal T, Boyett MR, Morris GM. The anatomy and physiology of the sinoatrial node--a contemporary review. Pacing Clin Electrophysiol PACE. 2010;33(11):1392–406.PubMedCrossRef
18.
Boyett MR, Honjo H, Kodama I. The sinoatrial node, a heterogeneous pacemaker structure. Cardiovasc Res. 2000;47(4):658–87.PubMedCrossRef
19.
Fedorov VV, Glukhov AV, Chang R. Conduction barriers and pathways of the sinoatrial pacemaker complex: their role in normal rhythm and atrial arrhythmias. Am J Physiol Heart Circ Physiol. 2012;302(9):H1773–83.PubMedCrossRef
20.
Stieber J, Herrmann S, Feil S, Loster J, Feil R, Biel M, et al. The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart. Proc Natl Acad Sci. 2003;100(25):15235–40.PubMedPubMedCentralCrossRef
21.
Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. Nature. 1998;393(6685):587–91.PubMedCrossRef
22.
Sun Y, Liang X, Najafi N, Cass M, Lin L, Cai C-L, et al. Islet 1 is expressed in distinct cardiovascular lineages, including pacemaker and coronary vascular cells. Dev Biol. 2007;304(1):286–96.PubMedCrossRef
23.
Blaschke RJ, Hahurij ND, Kuijper S, Just S, Wisse LJ, Deissler K, et al. Targeted mutation reveals essential functions of the homeodomain transcription factor Shox2 in sinoatrial and pacemaking development. Circulation. 2007;115(14):1830–8.PubMedCrossRef
24.
Wiese C, Grieskamp T, Airik R, Mommersteeg MTM, Gardiwal A, de Gier-de Vries C, et al. Formation of the sinus node head and differentiation of sinus node myocardium are independently regulated by Tbx18 and Tbx3. Circ Res. 2009;104(3):388–97.PubMedCrossRef
25.
Marionneau C, Couette B, Liu J, Li H, Mangoni ME, Nargeot J, et al. Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart: ion channel expression in the murine heart. J Physiol. 2005;562(1):223–34.PubMedCrossRef
26.
Tellez JO, Dobrzynski H, Greener ID, Graham GM, Laing E, Honjo H, et al. Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit. Circ Res. 2006;99(12):1384–93.PubMedCrossRef
27.
Gaborit N, Le Bouter S, Szuts V, Varro A, Escande D, Nattel S, et al. Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart: regional ion channel subunit gene expression in the human heart. J Physiol. 2007;582(2):675–93.PubMedPubMedCentralCrossRef
28.
Liang X, Zhang Q, Cattaneo P, Zhuang S, Gong X, Spann NJ, et al. Transcription factor ISL1 is essential for pacemaker development and function. J Clin Invest. 2015;125(8):3256–68.PubMedPubMedCentralCrossRef
29.
Vedantham V, Galang G, Evangelista M, Deo RC, Srivastava D. RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells. Circ Res. 2015;116(5):797–803.PubMedPubMedCentralCrossRef
30.
•• van Eif VWW, Stefanovic S, van Duijvenboden K, Bakker M, Wakker V, de Gier-de Vries C, et al. Transcriptome analysis of mouse and human sinoatrial node cells reveals a conserved genetic program. Dev Camb Engl. 2019;146(8). This study elucidates a conserved genetic program between the mouse and human SAN using bulk RNA-seq, validating known markers and identifying novel genes such as SMOC2 and VSNL1 and allowing for the translation of knowledge obtained primarily in a murine model to the human SAN.
31.
Fedorov VV, Schuessler RB, Hemphill M, Ambrosi CM, Chang R, Voloshina AS, et al. Structural and functional evidence for discrete exit pathways that connect the canine sinoatrial node and atria. Circ Res. 2009;104(7):915–23.PubMedPubMedCentralCrossRef
32.
Sonneveld S, Verhagen BMP, Tanenbaum ME. Heterogeneity in mRNA translation. Trends Cell Biol. 2020 Aug;30(8):606–18.PubMedCrossRef
33.
• Linscheid N, Logantha SJRJ, Poulsen PC, Zhang S, Schrölkamp M, Egerod KL, et al. Quantitative proteomics and single-nucleus transcriptomics of the sinus node elucidates the foundation of cardiac pacemaking. Nat Commun. 2019;10(1):2889 Findings from this study present a detailed picture of the SAN by identifying cell type–specific differences in the transcriptome and proteome within the SAN and compared with surrounding atrial myocardium.PubMedPubMedCentralCrossRef
34.
van Weerd JH, Badi I, van den Boogaard M, Stefanovic S, van de Werken HJG, Gomez-Velazquez M, et al. A large permissive regulatory domain exclusively controls Tbx3 expression in the cardiac conduction system. Circ Res. 2014;115(4):432–41.PubMedCrossRef
35.
Fernandez-Perez A, Sathe AA, Bhakta M, Leggett K, Xing C, Munshi NV. Hand2 selectively reorganizes chromatin accessibility to induce pacemaker-like transcriptional reprogramming. Cell Rep. 2019;27(8):2354–2369.e7.PubMedPubMedCentralCrossRef
36.
• Galang G, Mandla R, Ruan H, Jung C, Sinha T, Stone NR, et al. ATAC-Seq reveals an Isl1 enhancer that regulates sinoatrial node development and function. Circ Res. 2020;127(12):1502–18 This study explores in vivo the epigenome of the SAN using bulk ATAC-seq to identify novel enhancers important for the unique gene regulatory program that drives SAN development and function. Importantly, a conserved enhancer region specific to ISL1 is hypothesized to play a key role in human SAN function.PubMedCrossRef
37.
• van Eif VWW, Protze SI, Bosada FM, Yuan X, Sinha T, van Duijvenboden K, et al. Genome-wide analysis identifies an essential human TBX3 pacemaker enhancer. Circ Res. 2020;127(12):1522–35 This study presents a genome-wide accessibility profile of the human SAN with a subset of pacemaker-specific regulatory elements validated in vivo, including a conserved enhancer region that drives the expression of TBX3 within the SAN.PubMedCrossRef
38.
Tawara S. Das Reizleitungssystem des Säugetierherzens; eine anatomisch-histologische Studie über das Atrioventrikularbündel und die Purkinjeschen Fäden. Jena: Fischer; 1906.
39.
Kurian T, Ambrosi C, Hucker W, Fedorov VV, Efimov IR. Anatomy and electrophysiology of the human AV node. Pacing Clin Electrophysiol PACE. 2010;33(6):754–62.PubMedCrossRef
40.
Meijler FL, Janse MJ. Morphology and electrophysiology of the mammalian atrioventricular node. Physiol Rev. 1988;68(2):608–47.PubMedCrossRef
41.
Inoue S, Becker AE. Posterior extensions of the human compact atrioventricular node: a neglected anatomic feature of potential clinical significance. Circulation. 1998;97(2):188–93.PubMedCrossRef
42.
Atkinson AJ, Logantha SJRJ, Hao G, Yanni J, Fedorenko O, Sinha A, et al. Functional, anatomical, and molecular investigation of the cardiac conduction system and arrhythmogenic atrioventricular ring tissue in the rat heart. J Am Heart Assoc. 2013;2(6):e000246.PubMedPubMedCentralCrossRef
43.
Bakker ML, Moorman AFM, Christoffels VM. The atrioventricular node: origin, development, and genetic program. Trends Cardiovasc Med. 2010;20(5):164–71.PubMedCrossRef
44.
Hoffman BF, De Carvalho AP, Mello WC, Cranefield PF. Electrical activity of single fibers of the atrioventricular node. Circ Res. 1959;7(1):11–8.PubMedCrossRef
45.
Billette J. Atrioventricular nodal activation during periodic premature stimulation of the atrium. Am J Phys. 1987;252(1 Pt 2):H163–77.
46.
Meijler FL, Janse MJ. Morphology and electrophysiology of the mammalian atrioventricular node. Physiol Rev. 1988;68(2):608–47.PubMedCrossRef
47.
Munk AA, Adjemian RA, Zhao J, Ogbaghebriel A, Shrier A. Electrophysiological properties of morphologically distinct cells isolated from the rabbit atrioventricular node. J Physiol. 1996;493(Pt 3):801–18.PubMedPubMedCentralCrossRef
48.
Coppen SR, Severs NJ, Gourdie RG. Connexin45 (alpha 6) expression delineates an extended conduction system in the embryonic and mature rodent heart. Dev Genet. 1999;24(1–2):82–90.PubMedCrossRef
49.
Yoo S, Dobrzynski H, Fedorov VV, Xu S-Z, Yamanushi TT, Jones SA, et al. Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat. Circulation. 2006;114(13):1360–71.PubMedCrossRef
50.
Coppen SR, Kaba RA, Halliday D, Dupont E, Skepper JN, Elneil S, et al. Comparison of connexin expression patterns in the developing mouse heart and human foetal heart. Mol Cell Biochem. 2003;242(1–2):121–7.PubMedCrossRef
51.
Aanhaanen WTJ, Brons JF, Domínguez JN, Rana MS, Norden J, Airik R, et al. The Tbx2+ primary myocardium of the atrioventricular canal forms the atrioventricular node and the base of the left ventricle. Circ Res. 2009;104(11):1267–74.PubMedCrossRef
52.
Hoogaars WMH, Tessari A, Moorman AFM, de Boer PAJ, Hagoort J, Soufan AT, et al. The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. Cardiovasc Res. 2004;62(3):489–99.PubMedCrossRef
53.
Singh R, Hoogaars WM, Barnett P, Grieskamp T, Rana MS, Buermans H, et al. Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation. Cell Mol Life Sci CMLS. 2012;69(8):1377–89.PubMedCrossRef
54.
Horsthuis T, Buermans HPJ, Brons JF, Verkerk AO, Bakker ML, Wakker V, et al. Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter. Circ Res. 2009;105(1):61–9.PubMedCrossRef
55.
Liang X, Evans SM, Sun Y. Insights into cardiac conduction system formation provided by HCN4 expression. Trends Cardiovasc Med. 2015;25(1):1–9.PubMedCrossRef
56.
Bakker ML, Boink GJJ, Boukens BJ, Verkerk AO, van den Boogaard M, den Haan AD, et al. T-box transcription factor TBX3 reprogrammes mature cardiac myocytes into pacemaker-like cells. Cardiovasc Res. 2012;94(3):439–49.PubMedCrossRef
57.
58.
Greener ID, Monfredi O, Inada S, Chandler NJ, Tellez JO, Atkinson A, et al. Molecular architecture of the human specialised atrioventricular conduction axis. J Mol Cell Cardiol. 2011;50(4):642–51.PubMedCrossRef
59.
Schram G, Pourrier M, Melnyk P, Nattel S. Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res. 2002;90(9):939–50.PubMedCrossRef
60.
Kreuzberg MM, Söhl G, Kim J-S, Verselis VK, Willecke K, Bukauskas FF. Functional properties of mouse connexin30.2 expressed in the conduction system of the heart. Circ Res. 2005;96(11):1169–77.PubMedPubMedCentralCrossRef
61.
Miquerol L, Bellon A, Moreno N, Beyer S, Meilhac SM, Buckingham M, et al. Resolving cell lineage contributions to the ventricular conduction system with a Cx40-GFP allele: a dual contribution of the first and second heart fields. Dev Dyn Off Publ Am Assoc Anat. 2013;242(6):665–77.
62.
Greener ID, Tellez JO, Dobrzynski H, Yamamoto M, Graham GM, Billeter R, et al. Ion channel transcript expression at the rabbit atrioventricular conduction axis. Circ Arrhythm Electrophysiol. 2009;2(3):305–15.PubMedCrossRef
63.
Horsthuis T, Buermans HPJ, Brons JF, Verkerk AO, Bakker ML, Wakker V, et al. Gene expression profiling of the forming atrioventricular node using a novel tbx3-based node-specific transgenic reporter. Circ Res. 2009;105(1):61–9.PubMedCrossRef
64.
Mohan RA, Bosada FM, van Weerd JH, van Duijvenboden K, Wang J, Mommersteeg MTM, et al. T-box transcription factor 3 governs a transcriptional program for the function of the mouse atrioventricular conduction system. Proc Natl Acad Sci U S A. 2020;117(31):18617–26.PubMedPubMedCentralCrossRef
65.
• Bhattacharyya S, Duan J, Wang L, Li B, Bhakta M, Fernandez-Perez A, et al. Using Gjd3-CreEGFP mice to examine atrioventricular node morphology and composition. Sci Rep. 2019;9(1):2106 This study presents a novel transgenic mouse model for improved characterization of AVN cellular heterogeneity using expression of a GFP reporter gene under the control of endogenous GJD3 regulatory elements without disrupting native expression. Application of this model enabled visualization and microdissection of the AVN and generation of a single-cell atlas of the AVN region.PubMedPubMedCentralCrossRef
66.
Mazgalev TN, Tchou PJ. Atrial-AV nodal electrophysiology: a view from the millennium. Hoboken: Wiley-Blackwell; 2000. First Edition.
67.
68.
Mangoni ME, Nargeot J. Genesis and regulation of the heart automaticity. Physiol Rev. 2008;88(3):919–82.PubMedCrossRef
69.
Miquerol L, Moreno-Rascon N, Beyer S, Dupays L, Meilhac SM, Buckingham ME, et al. Biphasic development of the mammalian ventricular conduction system. Circ Res. 2010;107(1):153–61.PubMedCrossRef
70.
Caref EB, Boutjdir M, Himel HD, El-Sherif N. Role of subendocardial Purkinje network in triggering torsade de pointes arrhythmia in experimental long QT syndrome. EP Eur. 2008;10(10):1218–23.
71.
Kang G, Giovannone SF, Liu N, Liu F-Y, Zhang J, Priori SG, et al. Purkinje cells from RyR2 mutant mice are highly arrhythmogenic but responsive to targeted therapy. Circ Res. 2010;107(4):512–9.PubMedPubMedCentralCrossRef
72.
Almehairi M, Alshiekh-Ali AA, Alfagih A. Idiopathic short-coupled ventricular tachyarrhythmias: systematic review and validation of electrocardiographic indices. Egypt Heart J. 2018;70(4):301–6.PubMedPubMedCentralCrossRef
73.
Garcia-Bustos V, Sebastian R, Izquierdo M, Molina P, Chorro FJ, Ruiz-Sauri A. A quantitative structural and morphometric analysis of the Purkinje network and the Purkinje-myocardial junctions in pig hearts. J Anat. 2017;230(5):664–78.PubMedPubMedCentralCrossRef
74.
Ono N, Yamaguchi T, Ishikawa H, Arakawa M, Takahashi N, Saikawa T, et al. Morphological varieties of the Purkinje fiber network in mammalian hearts, as revealed by light and electron microscopy. Arch Histol Cytol. 2009;72(3):139–49.PubMedCrossRef
75.
Romero D, Camara O, Sachse F, Sebastian R. Analysis of microstructure of the cardiac conduction system based on three-dimensional confocal microscopy. PLoS One. 2016;11(10):e0164093.PubMedPubMedCentralCrossRef
76.
Miquerol L, Meysen S, Mangoni M, Bois P, van Rijen HVM, Abran P, et al. Architectural and functional asymmetry of the His-Purkinje system of the murine heart. Cardiovasc Res. 2004;63(1):77–86.PubMedCrossRef
77.
Pallante BA, Giovannone S, Fang-Yu L, Zhang J, Liu N, Kang G, et al. Contactin-2 expression in the cardiac Purkinje fiber network. Circ Arrhythm Electrophysiol. 2010;3(2):186–94.PubMedPubMedCentralCrossRef
78.
Moskowitz IPG, Pizard A, Patel VV, Bruneau BG, Kim JB, Kupershmidt S, et al. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Dev Camb Engl. 2004;131(16):4107–16.
79.
Liang X, Wang G, Lin L, Lowe J, Zhang Q, Bu L, et al. HCN4 dynamically marks the first heart field and conduction system precursors. Circ Res. 2013;113(4):399–407.PubMedPubMedCentralCrossRef
80.
Delorme B, Dahl E, Jarry-Guichard T, Briand JP, Willecke K, Gros D, et al. Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system. Circ Res. 1997;81(3):423–37.PubMedCrossRef
81.
Arnolds DE, Liu F, Fahrenbach JP, Kim GH, Schillinger KJ, Smemo S, et al. TBX5 drives Scn5a expression to regulate cardiac conduction system function. J Clin Invest. 2012;122(7):2509–18.PubMedPubMedCentralCrossRef
82.
Zhang S-S, Kim K-H, Rosen A, Smyth JW, Sakuma R, Delgado-Olguín P, et al. Iroquois homeobox gene 3 establishes fast conduction in the cardiac His-Purkinje network. Proc Natl Acad Sci U S A. 2011;108(33):13576–81.PubMedPubMedCentralCrossRef
83.
Kim K-H, Rosen A, Hussein SMI, Puviindran V, Korogyi AS, Chiarello C, et al. Irx3 is required for postnatal maturation of the mouse ventricular conduction system. Sci Rep. 2016;6:19197.PubMedPubMedCentralCrossRef
84.
85.
Kim EE, Shekhar A, Lu J, Lin X, Liu F-Y, Zhang J, et al. PCP4 regulates Purkinje cell excitability and cardiac rhythmicity. J Clin Invest. 2014;124(11):5027–36.PubMedPubMedCentralCrossRef
86.
Shekhar A, Lin X, Liu F-Y, Zhang J, Mo H, Bastarache L, et al. Transcription factor ETV1 is essential for rapid conduction in the heart. J Clin Invest. 2016;126(12):4444–59.PubMedPubMedCentralCrossRef
87.
Shekhar A, Lin X, Lin B, Liu F-Y, Zhang J, Khodadadi-Jamayran A, et al. ETV1 activates a rapid conduction transcriptional program in rodent and human cardiomyocytes. Sci Rep. 2018;8(1):9944.PubMedPubMedCentralCrossRef
88.
Haissaguerre M, Vigmond E, Stuyvers B, Hocini M, Bernus O. Ventricular arrhythmias and the His-Purkinje system. Nat Rev Cardiol. 2016;13(3):155–66.PubMedCrossRef
89.
Herron TJ, Milstein ML, Anumonwo J, Priori SG, Jalife J. Purkinje cell calcium dysregulation is the cellular mechanism that underlies catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2010;7(8):1122–8.PubMedPubMedCentralCrossRef
90.
Clauss S, Bleyer C, Schüttler D, Tomsits P, Renner S, Klymiuk N, et al. Animal models of arrhythmia: classic electrophysiology to genetically modified large animals. Nat Rev Cardiol. 2019;16(8):457–75.PubMedCrossRef
91.
Brown SDM, Holmes CC, Mallon A-M, Meehan TF, Smedley D, Wells S. High-throughput mouse phenomics for characterizing mammalian gene function. Nat Rev Genet. 2018;19(6):357–70.PubMedPubMedCentralCrossRef
92.
Protze SI, Liu J, Nussinovitch U, Ohana L, Backx PH, Gepstein L, et al. Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker. Nat Biotechnol. 2017;35(1):56–68.PubMedCrossRef
93.
Marx V. Method of the year: spatially resolved transcriptomics. Nat Methods. 2021;18(1):9–14.PubMedCrossRef
94.
• Tucker NR, Chaffin M, Fleming SJ, Hall AW, Parsons VA, Bedi KC, et al. Transcriptional and cellular diversity of the human heart. Circulation. 2020;142(5):466–82 This study is the first to capture the transcriptional diversity of working human cardiomyocytes at single-cell resolution.PubMedCrossRef
95.
• Cao J, O’Day DR, Pliner HA, Kingsley PD, Deng M, Daza RM, et al. A human cell atlas of fetal gene expression. Science. 2020;370(6518). This study demonstrates the incredible utility of single-nuclear RNA sequencing to create an expansive developmental gene expression atlas derived from multiple human fetal tissues.
96.
• Domcke S, Hill AJ, Daza RM, Cao J, O’Day DR, Pliner HA, et al. A human cell atlas of fetal chromatin accessibility. Science. 2020;370(6518) Findings of this study allow for the correlation of transcriptional and epigenetic profiles to identify tissue- and cell type–specific regulatory elements that drive the formation of unique genetic programs.
Metadaten
Titel
Molecular Profiling of the Cardiac Conduction System: the Dawn of a New Era
verfasst von
Sruthi Mantri
Sean M. Wu
William R. Goodyer
Publikationsdatum
01.08.2021
Verlag
Springer US
Erschienen in
Current Cardiology Reports / Ausgabe 8/2021
Print ISSN: 1523-3782
Elektronische ISSN: 1534-3170
DOI
https://doi.org/10.1007/s11886-021-01536-w

Weitere Artikel der Ausgabe 8/2021

Current Cardiology Reports 8/2021 Zur Ausgabe

Structural Heart Disease (RJ Siegel and NC Wunderlich, Section Editors)

How to Image and Manage Prosthesis-Related Complications After Transcatheter Aortic Valve Replacement

Cardio-Oncology (TG Neilan, Section Editor)

Cardiovascular Toxicity of Androgen Deprivation Therapy

Diabetes and Cardiovascular Disease (D Bruemmer, Section Editor)

Weight Management Strategies for the Patient with Diabetes

Nuclear Cardiology (V Dilsizian, Section Editor)

PET Imaging of Post-infarct Myocardial Inflammation

Cardiovascular Genomics (P Natarajan, Section Editor)

Monogenic and Polygenic Models of Coronary Artery Disease

Cardiac PET, CT, and MRI (P Schoenhagen and P-H Chen, Section Editors)

Anomalous Coronary Arteries: When to Follow-up, Risk Stratify, and Plan Intervention

Neu im Fachgebiet Kardiologie

Das Risiko für Vorhofflimmern in der Bevölkerung steigt

02.05.2024 Vorhofflimmern Nachrichten

Das Risiko, im Lauf des Lebens an Vorhofflimmern zu erkranken, ist in den vergangenen 20 Jahren gestiegen: Laut dänischen Zahlen wird es drei von zehn Personen treffen. Das hat Folgen weit über die Schlaganfallgefährdung hinaus.

VHF-Ablation nützt wohl nur bei reduzierter Auswurfleistung

02.05.2024 Ablationstherapie Nachrichten

Ob die Katheterablation von Vorhofflimmern bei Patienten mit Herzinsuffizienz die Komplikationsraten senkt, scheint davon abzuhängen, ob die Auswurfleistung erhalten ist oder nicht. Das legen die Ergebnisse einer Metaanalyse nahe.

Weniger Extremitätenischämien mit dualer Plättchenhemmung

02.05.2024 Thrombozytenaggregationshemmer Nachrichten

Eine Behandlung mit Ticagrelor zusätzlich zu ASS kann das Risiko für Revaskularisierungen und Amputationen von Extremitäten bei Diabetikern mit stabiler KHK deutlich reduzieren, vor allem für solche mit PAVK. Dafür spricht eine Auswertung der Interventionsstudie THEMIS.

Endlich: Zi zeigt, mit welchen PVS Praxen zufrieden sind

IT für Ärzte Nachrichten

Darauf haben viele Praxen gewartet: Das Zi hat eine Liste von Praxisverwaltungssystemen veröffentlicht, die von Nutzern positiv bewertet werden. Eine gute Grundlage für wechselwillige Ärzte und Psychotherapeuten.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise