ArticleThe Journal of biological chemistry2010
Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Molecular gatekeepers of endogenous adult mammalian cardiomyocyte proliferation.Nature reviews. Cardiology · 2025Review
- Association of the rs3039851 Insertion/Deletion in the GeneBiomedicines · 2023Article
- A cellular atlas of calcineurin signaling.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Endothelial Cell GATA2 Modulates the Cardiomyocyte Stress Response through the Regulation of Two Long Non-Coding RNAs.Biology · 2022Article
- Targeting calcineurin induces cardiomyocyte proliferation in adult mice.Nature cardiovascular research · 2022Article
- Calcineurin in the heart: New horizons for an old friend.Cellular signalling · 2021Review
- A Review of Calcineurin Biophysics with Implications for Cardiac Physiology.International journal of molecular sciences · 2021Review
- Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.Molecular cell · 2020Article
- Mechanisms of physiological and pathological cardiac hypertrophy.Nature reviews. Cardiology · 2018Review
- Reduced CardiacCirculation. Cardiovascular genetics · 2017Article
- Calcineurin signaling in the heart: The importance of time and place.Journal of molecular and cellular cardiology · 2017Review
- Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Article
- MBNL1-mediated regulation of differentiation RNAs promotes myofibroblast transformation and the fibrotic response.Nature communications · 2015Article
- Cardiac-specific deletion of protein phosphatase 1β promotes increased myofilament protein phosphorylation and contractile alterations.Journal of molecular and cellular cardiology · 2015Article
- Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis.The Journal of clinical investigation · 2015Article
- Na(+)/H (+) exchanger isoform 1 induced osteopontin expression in cardiomyocytes involves NFAT3/Gata4.Molecular and cellular biochemistry · 2015Article
- Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling.Circulation. Heart failure · 2015Article
- NFAT as cancer target: mission possible?Biochimica et biophysica acta · 2014Review
- Galactokinase is a novel modifier of calcineurin-induced cardiomyopathy in Drosophila.Genetics · 2014Article
- Genetic deletion of the mitochondrial phosphate carrier desensitizes the mitochondrial permeability transition pore and causes cardiomyopathy.Cell death and differentiation · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Calcineurin is a protein phosphatase that is uniquely regulated by sustained increases in intracellular Ca(2+) following signal transduction events. Calcineurin controls cellular proliferation, differentiation, apoptosis, and inducible gene expression following stress and neuroendocrine stimulation. In the adult heart, calcineurin regulates hypertrophic growth of cardiomyocytes in response to pathologic insults that are associated with altered Ca(2+) handling. Here we determined that calcineurin signaling is directly linked to the proper control of cardiac contractility, rhythm, and the expression of Ca(2+)-handling genes in the heart. Our approach involved a cardiomyocyte-specific deletion using a CnB1-LoxP-targeted allele in mice and three different cardiac-expressing Cre alleles/transgenes. Deletion of calcineurin with the Nkx2.5-Cre knock-in allele resulted in lethality at 1 day after birth due to altered right ventricular morphogenesis, reduced ventricular trabeculation, septal defects, and valvular overgrowth. Slightly later deletion of calcineurin with the alpha-myosin heavy chain Cre transgene resulted in lethality in early mid adulthood that was characterized by substantial reductions in cardiac contractility, severe arrhythmia, and reduced myocyte content in the heart. Young calcineurin heart-deleted mice died suddenly after pressure overload stimulation or neuroendocrine agonist infusion, and telemetric monitoring of older mice showed arrhythmia leading to sudden death. Mechanistically, loss of calcineurin reduced expression of key Ca(2+)-handling genes that likely lead to arrhythmia and reduced contractility. Loss of calcineurin also directly impacted cellular proliferation in the postnatal developing heart. These results reveal multiple mechanisms whereby calcineurin regulates cardiac development and myocyte contractility.
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Registered trials
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