Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias

Man Liu; Gyeoung Jin Kang; Samuel C. Dudley

doi:10.1016/j.molmed.2022.03.006

Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias

Man Liu, Gyeoung Jin Kang, Samuel C. Dudley

Medicine - Cardiology Division

Research output: Contribution to journal › Review article › peer-review

4 Scopus citations

Abstract

Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.

Original language	English (US)
Pages (from-to)	443-451
Number of pages	9
Journal	Trends in Molecular Medicine
Volume	28
Issue number	6
DOIs	https://doi.org/10.1016/j.molmed.2022.03.006
State	Published - Jun 2022

Bibliographical note

Funding Information:
This work is supported by R01 HL104025 (SCD) and Rhode Island Foundation grant 20154145 (M.L.).

Publisher Copyright:
© 2022 Elsevier Ltd

Keywords

cardiac ion channel
heart failure
mRNA degradation
myocardial infarction
therapy

PubMed: MeSH publication types

Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

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10.1016/j.molmed.2022.03.006

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title = "Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias",

abstract = "Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.",

keywords = "cardiac ion channel, heart failure, mRNA degradation, myocardial infarction, therapy",

author = "Man Liu and Kang, {Gyeoung Jin} and Dudley, {Samuel C.}",

note = "Funding Information: This work is supported by R01 HL104025 (SCD) and Rhode Island Foundation grant 20154145 (M.L.). Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",

year = "2022",

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doi = "10.1016/j.molmed.2022.03.006",

language = "English (US)",

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T1 - Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias

AU - Liu, Man

AU - Kang, Gyeoung Jin

AU - Dudley, Samuel C.

PY - 2022/6

Y1 - 2022/6

N2 - Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.

AB - Cardiomyopathies are associated with arrhythmias and cardiac ion channel downregulation. This downregulation is arrhythmogenic. Paradoxically, antiarrhythmic therapies are based on ion channel-blocking drugs that further downregulate these channels and exhibit proarrhythmic risk. Recent studies have shown that inhibition of the protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) prevents select cardiac ion channel downregulation and plays a protective role against arrhythmias. Prevention of ion channel downregulation represents as a novel therapeutic strategy to treat arrhythmias in myocardial infarction and heart failure.

KW - cardiac ion channel

KW - heart failure

KW - mRNA degradation

KW - myocardial infarction

KW - therapy

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M3 - Review article

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JO - Trends in Molecular Medicine

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Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias

Abstract

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Keywords

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