ArticleEuropean heart journal2021
The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.
Article in European heart journal, 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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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
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- Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review).International journal of molecular medicine · 2025Review
- Molecular mechanisms and intervention approaches of heart failure (Review).International journal of molecular medicine · 2025Review
- Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis.Communications biology · 2025Article
- Human Umbilical Cord-Derived Mesenchymal Stem Cells-Exosomes-Delivered miR-375 Targets HDAC4 to Promote Autophagy and Suppress T Cell Apoptosis in Sepsis-Associated Acute Kidney Injury.Applied biochemistry and biotechnology · 2024Article
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Modulating autophagy to treat diseases: A revisited review on in silico methods.Journal of advanced research · 2024Review
- Crosstalk between myocardial autophagy and sterile inflammation in the development of heart failure.Autophagy reports · 2024Review
- Serum histone deacetylase 4 longitudinal change for estimating major adverse cardiovascular events in acute coronary syndrome patients receiving percutaneous coronary intervention.Irish journal of medical science · 2023Article
- Activation of AHR by ITE improves cardiac remodelling and function in rats after myocardial infarction.ESC heart failure · 2023Article
- Extracellular vesicles derived from different tissues attenuate cardiac dysfunction in murine MI models.Biology direct · 2023Article
- Porcupine inhibitor CGX1321 alleviates heart failure with preserved ejection fraction in mice by blocking WNT signaling.Acta pharmacologica Sinica · 2023Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- Downregulation of G protein-coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury.Kidney international · 2023Article
- Naringenin Attenuates Isoprenaline-Induced Cardiac Hypertrophy by Suppressing Oxidative Stress through the AMPK/NOX2/MAPK Signaling Pathway.Nutrients · 2023Article
- A Self-Sustaining Antioxidant Strategy for Effective Treatment of Myocardial Infarction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Molecular Mechanism and Therapeutic Strategy of Cardiorenal Syndrome Type 3.Reviews in cardiovascular medicine · 2023Review
- Cardioprotective effect of crude polysaccharide fermented by Trametes Sanguinea Lyoyd on doxorubicin-induced myocardial injury mice.BMC pharmacology & toxicology · 2023Article
- Article
- Comprehensive insights in GRK4 and hypertension: From mechanisms to potential therapeutics.Pharmacology & therapeutics · 2022Review
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17 authors at 2 institutions in 2 countries.
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Abstract
aimsG protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hypertension, but little is known about its role in cardiomyocytes and myocardial infarction (MI). The goal of present study is to explore the role of GRK4 in the pathogenesis and progression of MI. METHODS AND
resultsWe studied the expression and distribution pattern of GRK4 in mouse heart after MI. GRK4 A486V transgenic mice, inducible cardiomyocyte-specific GRK4 knockout mice, were generated and subjected to MI with their control mice. Cardiac infarction, cardiac function, cardiomyocyte apoptosis, autophagic activity, and HDAC4 phosphorylation were assessed. The mRNA and protein levels of GRK4 in the heart were increased after MI. Transgenic mice with the overexpression of human GRK4 wild type (WT) or human GRK4 A486V variant had increased cardiac infarction, exaggerated cardiac dysfunction and remodelling. In contrast, the MI-induced cardiac dysfunction and remodelling were ameliorated in cardiomyocyte-specific GRK4 knockout mice. GRK4 overexpression in cardiomyocytes aggravated apoptosis, repressed autophagy, and decreased beclin-1 expression, which were partially rescued by the autophagy agonist rapamycin. MI also induced the nuclear translocation of GRK4, which inhibited autophagy by increasing HDAC4 phosphorylation and decreasing its binding to the beclin-1 promoter. HDAC4 S632A mutation partially restored the GRK4-induced inhibition of autophagy. MI caused greater impairment of cardiac function in patients carrying the GRK4 A486V variant than in WT carriers.
conclusionGRK4 increases cardiomyocyte injury during MI by inhibiting autophagy and promoting cardiomyocyte apoptosis. These effects are mediated by the phosphorylation of HDAC4 and a decrease in beclin-1 expression.
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