ArticleCardiovascular research2015
Physiological activation of Akt by PHLPP1 deletion protects against pathological hypertrophy.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 63 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Exercise-induced cardiac hypertrophy: cellular and molecular mechanisms of cardiac adaptation following physical activity.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2026Review
- Ang-1 and VEGF: central regulators of angiogenesis.Molecular and cellular biochemistry · 2025Review
- Impact of Ionizing Radiation Exposure on Placental Function and Implications for Fetal Programming.International journal of molecular sciences · 2024Review
- miR-222 inhibits pathological cardiac hypertrophy and heart failure.Cardiovascular research · 2024Article
- Modulation of Heat Shock Protein Expression in Alveolar Adenocarcinoma Cells through Gold Nanoparticles and Cisplatin Treatment.Pharmaceutics · 2024Article
- PHLPP1 inhibits the growth and aerobic glycolysis activity of human ovarian granular cells through inactivating AKT pathway.BMC women's health · 2024Article
- Changes in glutamic oxaloacetic transaminase 2 during rat physiological and pathological cardiomyocyte hypertrophy.BMC cardiovascular disorders · 2023Article
- The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.Basic research in cardiology · 2023Review
- SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma.Molecules and cells · 2023Article
- Article
- PHLPP isoforms differentially regulate Akt isoforms and AS160 affecting neuronal insulin signaling and insulin resistance via Scribble.Cell communication and signaling : CCS · 2022Article
- METTL14 is required for exercise-induced cardiac hypertrophy and protects against myocardial ischemia-reperfusion injury.Nature communications · 2022Article
- PHLPP1 promotes neutral lipid accumulation through AMPK/ChREBP-dependent lipid uptake and fatty acid synthesis pathways.iScience · 2022Article
- Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?European journal of heart failure · 2022Review
- The female syndecan-4Frontiers in cell and developmental biology · 2022Article
- Construction of a diagnostic signature and immune landscape of pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2022Article
- Exercise-induced signaling pathways to counteracting cardiac apoptotic processes.Frontiers in cell and developmental biology · 2022Review
- On the PHLPPside: Emerging roles of PHLPP phosphatases in the heart.Cellular signalling · 2021Review
- Metal dependent protein phosphatase PPM family in cardiac health and diseases.Cellular signalling · 2021Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
aimsTo examine the role of physiological Akt signalling in pathological hypertrophy through analysis of PHLPP1 (PH domain leucine-rich repeat protein phosphatase) knock-out (KO) mice. METHODS AND
resultsTo investigate the in vivo requirement for 'physiological' control of Akt activation in cardiac growth, we examined the effect of deleting the Akt phosphatase, PHLPP, on the induction of cardiac hypertrophy. Basal Akt phosphorylation increased nearly two-fold in the cardiomyocytes from PHLPP1 KO mice and physiological hypertrophy induced by swimming exercise was accentuated as assessed by increased heart size and myocyte cell area. In contrast, the development of pathophysiological hypertrophy induced by pressure overload and assessed by increases in heart size, myocyte cell area, and hypertrophic gene expression was attenuated. This attenuation coincided with decreased fibrosis and cell death in the KO mice. Cast moulding revealed increased capillary density basally in the KO hearts, which was further elevated relative to wild-type mouse hearts in response to pressure overload. In vitro studies with isolated myocytes in co-culture also demonstrated that PHLPP1 deletion in cardiomyocytes can enhance endothelial tube formation. Expression of the pro-angiogenic factor VEGF was also elevated basally and accentuated in response to transverse aortic constriction in hearts from KO mice.
conclusionOur data suggest that enhancing Akt activity by inhibiting its PHLPP1-mediated dephosphorylation promotes processes associated with physiological hypertrophy that may be beneficial in attenuating the development of pathological hypertrophy.
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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.