ArticleJournal of cellular and molecular medicine2015
Class III PI3K-mediated prolonged activation of autophagy plays a critical role in the transition of cardiac hypertrophy to heart failure.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Exploring Phosphatase and Tensin Homologue Deleted on Chromosome Ten (PTEN) as a Potential Therapeutic Target for Cardiac Hypertrophy.ACS pharmacology & translational science · 2025Review
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Autophagy in Heart Failure: Insights into Mechanisms and Therapeutic Implications.Journal of cardiovascular development and disease · 2023Review
- The Transcription Factor EB (TFEB) Sensitizes the Heart to Chronic Pressure Overload.International journal of molecular sciences · 2022Article
- Construction of PIK3C3 Transgenic Pig and Its Pathogenesis of Liver Damage.Life (Basel, Switzerland) · 2022Article
- Tripartite motif 27 promotes cardiac hypertrophy via PTEN/Akt/mTOR signal pathways.Bioengineered · 2022Article
- Role of adiponectin in osteoarthritis.Frontiers in cell and developmental biology · 2022Review
- Exploring Key Genes and Pathways of Cardiac Hypertrophy Based on Bioinformatics.Disease markers · 2022Article
- Role of PI3K/Akt signaling pathway in cardiac fibrosis.Molecular and cellular biochemistry · 2021Review
- Mechanism of lncRNA-ANRIL/miR-181b in autophagy of cardiomyocytes in mice with uremia by targeting ATG5.PloS one · 2021Article
- MBNL1 regulates isoproterenol-induced myocardial remodelling in vitro and in vivo.Journal of cellular and molecular medicine · 2021Article
- Traditional Chinese Medicine Targeting Heat Shock Proteins as Therapeutic Strategy for Heart Failure.Frontiers in pharmacology · 2021Review
- Exercise-mediated regulation of autophagy in the cardiovascular system.Journal of sport and health science · 2020Review
- PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020Review
- Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy.Oxidative medicine and cellular longevity · 2020Review
- Beneficial effects of andrographolide in a rat model of autoimmune myocarditis and its effects on PI3K/Akt pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2019Article
- MicroRNA-based therapeutics in central nervous system injuries.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- The role of autophagy in advanced glycation end product-induced proliferation and migration in rat vascular smooth muscle cells.Iranian journal of basic medical sciences · 2018Article
- Balancing Autophagy for a Healthy Heart.Current opinion in physiology · 2018Article
- Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity.Journal of cellular and molecular medicine · 2017Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Pathological cardiac hypertrophy often leads to heart failure. Activation of autophagy has been shown in pathological hypertrophic hearts. Autophagy is regulated positively by Class III phosphoinositide 3-kinase (PI3K). However, it is unknown whether Class III PI3K plays a role in the transition of cardiac hypertrophy to heart failure. To address this question, we employed a previously established cardiac hypertrophy model in heat shock protein 27 transgenic mice which shares common features with several types of human cardiomyopathy. Age-matched wild-type mice served as control. Firstly, a prolonged activation of autophagy, as reflected by autophagosome accumulation, increased LC3 conversion and decreased p62 protein levels, was detected in hypertrophic hearts from adaptive stage to maladaptive stage. Moreover, morphological abnormalities in myofilaments and mitochondria were presented in the areas accumulated with autophagosomes. Secondly, activation of Class III PI3K Vacuolar protein sorting 34 (Vps34), as demonstrated by upregulation of Vps34 expression, increased interaction of Vps34 with Beclin-1, and deceased Bcl-2 expression, was demonstrated in hypertrophic hearts from adaptive stage to maladaptive stage. Finally, administration with Wortmaninn, a widely used autophagy inhibitor by suppressing Class III PI3K activity, significantly decreased autophagy activity, improved morphologies of intracellular apartments, and most importantly, prevented progressive cardiac dysfunction in hypertrophic hearts. Collectively, we demonstrated that Class III PI3K plays a central role in the transition of cardiac hypertrophy to heart failure via a prolonged activation of autophagy in current study. Class III PI3K may serve as a potential target for the treatment and management of maladaptive cardiac 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.