ArticleJournal of molecular and cellular cardiology2009
The role of Akt/GSK-3beta signaling in familial hypertrophic cardiomyopathy.
Article in Journal of molecular and cellular cardiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- An Assessment of the Therapeutic Landscape for the Treatment of Heart Disease in the RASopathies.Cardiovascular drugs and therapy · 2023Review
- Acute Glycogen Synthase Kinase-3 Inhibition Modulates Human Cardiac Conduction.JACC. Basic to translational science · 2022Article
- Exercise training maintains cardiovascular health: signaling pathways involved and potential therapeutics.Signal transduction and targeted therapy · 2022Review
- Low-dose Dasatinib Ameliorates Hypertrophic Cardiomyopathy in Noonan Syndrome with Multiple Lentigines.Cardiovascular drugs and therapy · 2022Article
- Obesity, not a high fat, high sucrose diet alone, induced glucose intolerance and cardiac dysfunction during pregnancy and postpartum.Scientific reports · 2021Article
- Dilated cardiomyopathy mutations in thin-filament regulatory proteins reduce contractility, suppress systolic CaAmerican journal of physiology. Heart and circulatory physiology · 2020Article
- Advanced Evolution of Pathogenesis Concepts in Cardiomyopathies.Journal of clinical medicine · 2019Review
- ATF6 Regulates Cardiac Hypertrophy by Transcriptional Induction of the mTORC1 Activator, Rheb.Circulation research · 2019Article
- Pregnancy late in rodent life has detrimental effects on the heart.American journal of physiology. Heart and circulatory physiology · 2018Article
- Article
- A Review of the Molecular Mechanisms Underlying the Development and Progression of Cardiac Remodeling.Oxidative medicine and cellular longevity · 2017Review
- Article
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
- Dual specificity phosphatase 4 mediates cardiomyopathy caused by lamin A/C (LMNA) gene mutation.The Journal of biological chemistry · 2012Article
- Akt and MAPK signaling mediate pregnancy-induced cardiac adaptation.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
- Article
- The cell biology of disease: cellular mechanisms of cardiomyopathy.The Journal of cell biology · 2011Review
- Abnormal heart rate regulation in murine hearts with familial hypertrophic cardiomyopathy-related cardiac troponin T mutations.American journal of physiology. Heart and circulatory physiology · 2011Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Mutations in cardiac troponin T (TnT) are a cause of familial hypertrophic cardiomyopathy (FHC). Transgenic mice expressing a missense mutation (R92Q) or a splice site donor mutation (Trunc) in the cardiac TnT gene have mutation-specific phenotypes but mice of both models have smaller hearts compared to wild type and exhibit hemodynamic dysfunction. Because growth-related signaling pathways in the hearts of mice expressing TnT mutations are not known, we evaluated the impact of increased Akt or glycogen synthase kinase-3beta (GSK-3beta) activity in both mutant TnT mice; molecules that increase heart size via physiologic pathways and block pathologic growth, respectively. Expression of activated Akt dramatically augments heart size in both R92Q and Trunc mice; however, this increase in heart size is not beneficial, since Akt also increases fibrosis in both TnT mutants and causes some pathologic gene expression shifts in the R92Q mice. Activated GSK-3beta results in further decreases in left ventricular size in both R92Q and Trunc hearts, but this decrease is associated with significant mutation-specific phenotypes. Among many pathologic consequences, activating GSK-3beta in R92Q hearts decreases phosphorylation of troponin I and results in early mortality. In contrast, increased GSK-3beta activity in Trunc hearts does not significantly impact cardiac phenotypes. These findings demonstrate that increased Akt and its downstream target, GSK-3beta can impact both cardiac size and phenotype in a mutation-specific manner. Moreover, increased activity of these molecules implicated in beneficial cardiac phenotypes exacerbates the progression of disease in the R92Q TnT mutant.
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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.