ArticleThe Journal of clinical investigation2006
TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 1 of them a synthesis that pooled it.
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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
262 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Meta-Analysis of Mechano-Sensitive Ion Channels in Human Hearts: Chamber- and Disease-Preferential mRNA Expression.International journal of molecular sciences · 2023Pooled it
- Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients.PloS one · 2014Trial
- Cardiomyocyte-Specific Smad7 Protects the Pressure-Overloaded Heart, Inhibiting the Transforming Growth Factor-β Receptor 1/Smad2/3 Cascade.Journal of the American Heart Association · 2026Article
- Cardiac mechanotransduction from development to disease.APL bioengineering · 2026Review
- Staple oligomers induce a stable RNA G-quadruplex structure for protein translation inhibition in therapeutics.Nature biomedical engineering · 2026Article
- Article
- Gain-of-Function VariantCirculation. Genomic and precision medicine · 2026Article
- Review
- The Potential Connection Between Mechanical Stress and Heart Failure with Preserved Ejection Fraction: Mechanistic Insights and Therapeutic Potential.International journal of medical sciences · 2026Review
- TRPC6 Deficiency Attenuates Mitochondrial and Cardiac Dysfunction in Heart Failure with Preserved Ejection Fraction Induced by High-Fat Diet Plus L-NAME.International journal of molecular sciences · 2025Article
- Flufenamic acid reduces alveolar bone loss and pyrazole 3 enhances alveolar bone recovery in periodontitis mice.Journal of veterinary science · 2025Article
- Soluble β-Amyloid Oligomers Selectively Upregulate TRPC3 in Excitatory Neurons via Calcineurin-Coupled NFAT.Cells · 2025Article
- Left ventricular flow dynamics by cardiac imaging techniques in heart failure patients: state of the art.Cardiovascular ultrasound · 2025Review
- The Heart Is a Smart Pump: Mechanotransduction Mechanisms of the Frank-Starling Law and the Anrep Effect.Annual review of physiology · 2025Review
- TRP channels and breast cancer: the role of TRPs in the pathophysiological development.Frontiers in molecular biosciences · 2025Review
- Mast Cells Contribute to Pressure Overload-Induced Myocardial Hypertrophy by Upregulating TRPV4 via Histamine: Role of Ca2+/ CnA/NFATc3 Signaling Pathway.Current medical science · 2024Article
- Acute contact with profibrotic macrophages mechanically activates fibroblasts via αvβ3 integrin-mediated engagement of Piezo1.Science advances · 2024Article
- Epigenetic Modulation of GPER Expression in Gastric and Colonic Smooth Muscle of Male and Female Non-Obese Diabetic (NOD) Mice: Insights into H3K4me3 and H3K27ac Modifications.International journal of molecular sciences · 2024Article
- Transient Receptor Potential Canonical 5 (TRPC5): Regulation of Heart Rate and Protection against Pathological Cardiac Hypertrophy.Biomolecules · 2024Article
- Sensational site: the sodium pump ouabain-binding site and its ligands.American journal of physiology. Cell physiology · 2024Review
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of beta-myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling.
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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.