ArticleThe Journal of clinical investigation2021
Inhibition of the unfolded protein response reduces arrhythmia risk after myocardial infarction.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Thbs1Journal of advanced research · 2026Article
- Cardiac Sodium Channel Regulation: A Potential New Therapeutic Target in Cardiomyopathy.Circulation research · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Stress-Induced Down-Regulation of CPEB4 Disrupts Sodium Channel Regulation and Myocardial Excitability.JACC. Basic to translational science · 2026Article
- Rg1-Loaded Tetrahedral DNA Nanostructures Attenuate Myocardial Ischemia-Reperfusion Injury by Suppressing Oxidative and Endoplasmic Reticulum Stress.International journal of nanomedicine · 2026Article
- NMDA-Type Glutamate Receptor Activation Promotes Ischemic Arrhythmias by Targeting the AKT1-TBX3-Nav1.5 Axis.Acta physiologica (Oxford, England) · 2025Article
- CDR1as modulates arrhythmia post-myocardial infarction via regulating Cav1.2.Acta biochimica et biophysica Sinica · 2025Article
- The Role of Infarct Border Zone Remodelling in Ventricular Arrhythmias: Bridging Basic Research and Clinical Applications.Journal of cellular and molecular medicine · 2025Review
- One day of environment-induced heat stress damages the murine myocardium.American journal of physiology. Heart and circulatory physiology · 2024Article
- Long non-coding RNA-mediated modulation of endoplasmic reticulum stress under pathological conditions.Journal of cellular and molecular medicine · 2024Review
- Cardiac-specific deletion of BRG1 ameliorates ventricular arrhythmia in mice with myocardial infarction.Acta pharmacologica Sinica · 2024Article
- The cGAS-STING/PERK-eIF2α: Individual or Potentially Collaborative Signaling Transduction in Cardiovascular Diseases.International journal of biological sciences · 2024Review
- KCNH2A561V Heterozygous Mutation Inhibits KCNH2 Protein Expression via The Activation of UPR Mediated by ATF6.Physiological research · 2023Article
- miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.Heart rhythm · 2023Article
- Heterogeneity of Repolarization and Cell-Cell Variability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility.Circulation. Arrhythmia and electrophysiology · 2023Article
- Chinese herbal medicine and active ingredients for diabetic cardiomyopathy: molecular mechanisms regulating endoplasmic reticulum stress.Frontiers in pharmacology · 2023Review
- Editorial: The role of calcium and calcium binding proteins in cell physiology and disease.Frontiers in physiology · 2023Article
- Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias.Trends in molecular medicine · 2022Review
- Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.Circulation research · 2022Article
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels. When activated, the protein kinase-like ER kinase (PERK) branch of the UPR reduces protein translation and abundance. We hypothesized that PERK inhibition could prevent ion channel downregulation and reduce arrhythmia risk after myocardial infarct (MI). MI induced in mice by coronary artery ligation resulted in reduced ion channel levels, ventricular tachycardia (VT), and prolonged corrected intervals between the Q and T waves on the ECGs (QTc). Protein levels of major cardiac ion channels were decreased. MI cardiomyocytes showed significantly prolonged action potential duration and decreased maximum upstroke velocity. Cardiac-specific PERK KO reduced electrical remodeling in response to MI, with shortened QTc intervals, fewer VT episodes, and higher survival rates. Pharmacological PERK inhibition had similar effects. In conclusion, we found that activated PERK during MI contributed to arrhythmia risk by the downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmia risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmia mechanism and that maintenance of ion channel levels is antiarrhythmic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.