ArticlePloS one2017
G protein-coupled receptor kinase 2 promotes cardiac hypertrophy.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Analysis of GRK2 aggregation in the pathology of Alzheimer disease in animal models.Cell reports. Medicine · 2026Article
- miR-181a post-transcriptionally targets GRK2 to limit maladaptive signaling in cardiomyocytes.Frontiers in cardiovascular medicine · 2026Article
- Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025Review
- Reversing cardiac hypertrophy and heart failure using a cardiac targeting peptide linked to miRNA106a.Clinical and translational medicine · 2025Article
- GRK2 and Mitochondrial Dynamics in Cardiovascular Health and Disease.International journal of molecular sciences · 2025Review
- Canonical or non-canonical, all aspects of G protein-coupled receptor kinase 2 in heart failure.Acta physiologica (Oxford, England) · 2025Review
- Active ingredients of traditional Chinese medicine inhibit NOD-like receptor protein 3 inflammasome: a novel strategy for preventing and treating heart failure.Frontiers in immunology · 2025Review
- Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression.International journal of molecular sciences · 2023Article
- Novel roles for G protein-coupled receptor kinases in cardiac injury and repair.Biochemical Society transactions · 2023Review
- The role of noncoding genetic variants in cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- GRK2 in cardiovascular disease and its potential as a therapeutic target.Journal of molecular and cellular cardiology · 2022Review
- GRK2 regulates ADP signaling in platelets via P2Y1 and P2Y12.Blood advances · 2022Article
- Reversing Cardiac Hypertrophy at the Source Using a Cardiac Targeting Peptide Linked to miRNA106a: Targeting Genes That Cause Cardiac Hypertrophy.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Functional resilience of C57BL/6J mouse heart to dietary fat overload.American journal of physiology. Heart and circulatory physiology · 2021Article
- Article
- Generation of Highly Selective, Potent, and Covalent G Protein-Coupled Receptor Kinase 5 Inhibitors.Journal of medicinal chemistry · 2021Article
- Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging.American journal of physiology. Heart and circulatory physiology · 2020Article
- DSCAM-AS1 mediates pro-hypertrophy role of GRK2 in cardiac hypertrophy aggravation via absorbing miR-188-5p.In vitro cellular & developmental biology. Animal · 2020Article
- G protein-coupled receptor kinase 2 (GRK2) as a multifunctional signaling hub.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure. Inhibition of GRK2 improved cardiac function and survival and diminished cardiac remodeling in various animal heart failure models. The aim of the present study was to investigate the effects of GRK2 on cardiac hypertrophy and dissect potential molecular mechanisms. In mice we observed increased GRK2 mRNA and protein levels following transverse aortic constriction (TAC). Conditional GRK2 knockout mice showed attenuated hypertrophic response with preserved ventricular geometry 6 weeks after TAC operation compared to wild-type animals. In isolated neonatal rat ventricular cardiac myocytes stimulation with angiotensin II and phenylephrine enhanced GRK2 expression leading to enhanced signaling via protein kinase B (PKB or Akt), consecutively inhibiting glycogen synthase kinase 3 beta (GSK3β), such promoting nuclear accumulation and activation of nuclear factor of activated T-cells (NFAT). Cardiac myocyte hypertrophy induced by in vitro GRK2 overexpression increased the cytosolic interaction of GRK2 and phosphoinositide 3-kinase γ (PI3Kγ). Moreover, inhibition of PI3Kγ as well as GRK2 knock down prevented Akt activation resulting in halted NFAT activity and reduced cardiac myocyte hypertrophy. Our data show that enhanced GRK2 expression triggers cardiac hypertrophy by GRK2-PI3Kγ mediated Akt phosphorylation and subsequent inactivation of GSK3β, resulting in enhanced NFAT activity.
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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.