RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissionsoup.com..
AIMS: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN. The aim of this study is to assess the role of RHOA-ROCK signalling in SAN development in the chicken heart.
METHODS AND RESULTS: ROCK signalling was inhibited chemically in embryonic chicken hearts using Y-27632. This prolonged the immature state of the sinus venosus myocardium, evidenced by up-regulation of the transcription factor ISL1, wide distribution of pacemaker potential, and significantly reduced heart rate. Furthermore ROCK inhibition caused aberrant expression of typical SAN genes: ROCK1, ROCK2, SHOX2, TBX3, TBX5, ISL1, HCN4, CX40, CAV3.1, and NKX2.5 and left-right asymmetry genes: PITX2C and NODAL. Anatomical abnormalities in pulmonary vein development were also observed. Patch clamp electrophysiology confirmed the immature phenotype of the SAN cells and a residual left-sided sinus venosus myocardium pacemaker-like potential.
CONCLUSIONS: RHOA-ROCK signalling is involved in establishing the right-sided SAN as the definitive pacemaker of the heart and restricts typical pacemaker gene expression to the right side of the sinus venosus myocardium.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:113 |
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| Enthalten in: |
Cardiovascular research - 113(2017), 10 vom: 01. Aug., Seite 1186-1197 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vicente-Steijn, Rebecca [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.05.2018 Date Revised 16.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/cvr/cvx104 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM27569951X |
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| 100 | 1 | |a Vicente-Steijn, Rebecca |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node |
| 264 | 1 | |c 2017 | |
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| 500 | |a Date Completed 21.05.2018 | ||
| 500 | |a Date Revised 16.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a AIMS: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN. The aim of this study is to assess the role of RHOA-ROCK signalling in SAN development in the chicken heart | ||
| 520 | |a METHODS AND RESULTS: ROCK signalling was inhibited chemically in embryonic chicken hearts using Y-27632. This prolonged the immature state of the sinus venosus myocardium, evidenced by up-regulation of the transcription factor ISL1, wide distribution of pacemaker potential, and significantly reduced heart rate. Furthermore ROCK inhibition caused aberrant expression of typical SAN genes: ROCK1, ROCK2, SHOX2, TBX3, TBX5, ISL1, HCN4, CX40, CAV3.1, and NKX2.5 and left-right asymmetry genes: PITX2C and NODAL. Anatomical abnormalities in pulmonary vein development were also observed. Patch clamp electrophysiology confirmed the immature phenotype of the SAN cells and a residual left-sided sinus venosus myocardium pacemaker-like potential | ||
| 520 | |a CONCLUSIONS: RHOA-ROCK signalling is involved in establishing the right-sided SAN as the definitive pacemaker of the heart and restricts typical pacemaker gene expression to the right side of the sinus venosus myocardium | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Arrhythmia | |
| 650 | 4 | |a Bradycardia | |
| 650 | 4 | |a Cardiac conduction system | |
| 650 | 4 | |a Heart development | |
| 650 | 4 | |a Sinus node dysfunction | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a rho-Associated Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a rhoA GTP-Binding Protein |2 NLM | |
| 650 | 7 | |a EC 3.6.5.2 |2 NLM | |
| 700 | 1 | |a Kelder, Tim P |e verfasserin |4 aut | |
| 700 | 1 | |a Tertoolen, Leon G |e verfasserin |4 aut | |
| 700 | 1 | |a Wisse, Lambertus J |e verfasserin |4 aut | |
| 700 | 1 | |a Pijnappels, Daniël A |e verfasserin |4 aut | |
| 700 | 1 | |a Poelmann, Robert E |e verfasserin |4 aut | |
| 700 | 1 | |a Schalij, Martin J |e verfasserin |4 aut | |
| 700 | 1 | |a deRuiter, Marco C |e verfasserin |4 aut | |
| 700 | 1 | |a Gittenberger-de Groot, Adriana C |e verfasserin |4 aut | |
| 700 | 1 | |a Jongbloed, Monique R M |e verfasserin |4 aut | |
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