MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel
Cardiac ischemia is associated with arrhythmias; however, effective therapies are currently limited. The cardiac voltage-gated sodium channel α subunit (SCN5A), encoding the Nav1.5 current, plays a key role in the cardiac electrical conduction and arrhythmic risk. Here, we show that hypoxia reduces Nav1.5 through effects on a miR, miR-448. miR-448 expression is increased in ischemic cardiomyopathy. miR-448 has a conserved binding site in 3'-UTR of SCN5A. miR-448 binding to this site suppressed SCN5A expression and sodium currents. Hypoxia-induced HIF-1α and NF-κB were major transcriptional regulators for MIR448. Moreover, hypoxia relieved MIR448 transcriptional suppression by RE1 silencing transcription factor. Therefore, miR-448 inhibition reduced arrhythmic risk after myocardial infarction. Here, we show that ischemia drove miR-448 expression, reduced Nav1.5 current, and increased arrhythmic risk. Arrhythmic risk was improved by preventing Nav1.5 downregulation, suggesting a new approach to antiarrhythmic therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
JCI insight - 5(2020), 23 vom: 03. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Gyeoung-Jin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.05.2021 Date Revised 24.05.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.140759 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM316770418 |
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| 100 | 1 | |a Kang, Gyeoung-Jin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a MIR448 antagomir reduces arrhythmic risk after myocardial infarction by upregulating the cardiac sodium channel |
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| 500 | |a Date Revised 24.05.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Cardiac ischemia is associated with arrhythmias; however, effective therapies are currently limited. The cardiac voltage-gated sodium channel α subunit (SCN5A), encoding the Nav1.5 current, plays a key role in the cardiac electrical conduction and arrhythmic risk. Here, we show that hypoxia reduces Nav1.5 through effects on a miR, miR-448. miR-448 expression is increased in ischemic cardiomyopathy. miR-448 has a conserved binding site in 3'-UTR of SCN5A. miR-448 binding to this site suppressed SCN5A expression and sodium currents. Hypoxia-induced HIF-1α and NF-κB were major transcriptional regulators for MIR448. Moreover, hypoxia relieved MIR448 transcriptional suppression by RE1 silencing transcription factor. Therefore, miR-448 inhibition reduced arrhythmic risk after myocardial infarction. Here, we show that ischemia drove miR-448 expression, reduced Nav1.5 current, and increased arrhythmic risk. Arrhythmic risk was improved by preventing Nav1.5 downregulation, suggesting a new approach to antiarrhythmic therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Arrhythmias | |
| 650 | 4 | |a Cardiology | |
| 650 | 4 | |a Sodium channels | |
| 650 | 4 | |a hypoxia | |
| 650 | 7 | |a Antagomirs |2 NLM | |
| 650 | 7 | |a MIRN448 microRNA, human |2 NLM | |
| 650 | 7 | |a MIRN448 microRNA, mouse |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a NAV1.5 Voltage-Gated Sodium Channel |2 NLM | |
| 650 | 7 | |a SCN5A protein, human |2 NLM | |
| 650 | 7 | |a Sodium |2 NLM | |
| 650 | 7 | |a 9NEZ333N27 |2 NLM | |
| 700 | 1 | |a Xie, An |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Dudley, Samuel C |c Jr |e verfasserin |4 aut | |
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