ArticleThe Journal of clinical investigation2014
Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05993585 (The Effects of Cardiac Resynchronisation Therapy on the Frank Starling Mechanism in Patients With Heart Failure), which is not on this map. Cited by 48 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.
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.
The Effects of Cardiac Resynchronisation Therapy on the Frank Starling Mechanism in Patients With Heart Failure
Who cites it
48 citing papers in PubMed, 84 citations in OpenAlex.
- Proteomic Remodeling in the Failing Left Ventricle Adapting to Dyssynchrony.Proteomics. Clinical applications · 2026Article
- Severe obesity in human HFpEF alters contractile protein function and organization.Science (New York, N.Y.) · 2026Article
- Mechanisms of protein degradation in atrophying muscles: What have we learned during the past decade?The Journal of biological chemistry · 2026Review
- Protein biomarkers associated with left bundle branch block in patients with heart failure and reduced ejection fraction.ESC heart failure · 2026Article
- GSK3β-driven phosphorylation of ABLIM1 regulates its interactions with titin cardiac muscle.The Journal of general physiology · 2025Article
- S-Nitrosylation in Cardiovascular Disorders: The State of the Art.Biomolecules · 2025Review
- Concepts of Cardiac Dyssynchrony and Dynamic Approach.Diagnostics (Basel, Switzerland) · 2024Review
- Determination of Serum Glycogen Synthase 3 Beta Levels in Patients with Heart Failure, a Novel Marker for Diagnosis and Defining Disease Severity?Arquivos brasileiros de cardiologia · 2024Article
- miR-455-5p promotes pathological cardiac remodeling via suppression of PRMT1-mediated Notch signaling pathway.Cellular and molecular life sciences : CMLS · 2023Article
- GSK-3 at the heart of cardiometabolic diseases: Isoform-specific targeting is critical to therapeutic benefit.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- Dyssynchrony and resynchronization in heart failure-effects on regional and global gene expression in a murine pacemaker model.European heart journal open · 2023Article
- Peptidyl arginine deiminase inhibition alleviates angiotensin II-induced fibrosis.American journal of translational research · 2023Article
- Glycation of ryanodine receptor in circulating lymphocytes predicts the response to cardiac resynchronization therapy.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022Article
- GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation.Circulation research · 2022Article
- PDE1 Inhibition Modulates CaCirculation research · 2021Article
- BAG3 expression and sarcomere localization in the human heart are linked to HSF-1 and are differentially affected by sex and disease.American journal of physiology. Heart and circulatory physiology · 2021Article
- Cardiomyocyte contractile impairment in heart failure results from reduced BAG3-mediated sarcomeric protein turnover.Nature communications · 2021Article
- The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down-regulation and mitochondrial dynamics alteration.Journal of cellular and molecular medicine · 2019Article
- Cardiomyocyte-GSK-3α promotes mPTP opening and heart failure in mice with chronic pressure overload.Journal of molecular and cellular cardiology · 2019Article
- Unraveling obscurins in heart disease.Pflugers Archiv : European journal of physiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Cardiac resynchronization therapy (CRT), the application of biventricular stimulation to correct discoordinate contraction, is the only heart failure treatment that enhances acute and chronic systolic function, increases cardiac work, and reduces mortality. Resting myocyte function also increases after CRT despite only modest improvement in calcium transients, suggesting that CRT may enhance myofilament calcium responsiveness. To test this hypothesis, we examined adult dogs subjected to tachypacing-induced heart failure for 6 weeks, concurrent with ventricular dyssynchrony (HF(dys)) or CRT. Myofilament force-calcium relationships were measured in skinned trabeculae and/or myocytes. Compared with control, maximal calcium-activated force and calcium sensitivity declined globally in HF(dys); however, CRT restored both. Phosphatase PP1 induced calcium desensitization in control and CRT-treated cells, while HF(dys) cells were unaffected, implying that CRT enhances myofilament phosphorylation. Proteomics revealed phosphorylation sites on Z-disk and M-band proteins, which were predicted to be targets of glycogen synthase kinase-3β (GSK-3β). We found that GSK-3β was deactivated in HF(dys) and reactivated by CRT. Mass spectrometry of myofilament proteins from HF(dys) animals incubated with GSK-3β confirmed GSK-3β–dependent phosphorylation at many of the same sites observed with CRT. GSK-3β restored calcium sensitivity in HF(dys), but did not affect control or CRT cells. These data indicate that CRT improves calcium responsiveness of myofilaments following HF(dys) through GSK-3β reactivation, identifying a therapeutic approach to enhancing contractile function
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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.