ArticleThe Journal of clinical investigation2005
PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury.
Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 120 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
120 citing papers in PubMed, 230 citations in OpenAlex.
- ABCC9 knockdown attenuates isoproterenol‑induced myocardial hypertrophy by inhibiting the PI3K/AKT signaling pathway.Molecular medicine reports · 2026Article
- Senescence-related epicardial adipocyte genes lead to immune infiltration and myocardial infarction progression.Frontiers in cardiovascular medicine · 2026Article
- Deciphering the role of crucial miRNAs involved in diabetic cardiomyopathy through a multiomics approach.Scientific reports · 2025Article
- Athlete's Heart Revisited: Historical, Clinical, and Molecular Perspectives.Circulation research · 2025Review
- Bone-marrow macrophage-derived GPNMB protein binds to orphan receptor GPR39 and plays a critical role in cardiac repair.Nature cardiovascular research · 2024Article
- Inhibition of the protective effects of preconditioning in ischemia-reperfusion injury by chronic methadone: the role of pAkt and pSTAT3.Scientific reports · 2024Article
- Caboxamycin Inhibits Heart Inflammation in a Coxsackievirus B3-Induced Myocarditis Mouse Model.Viruses · 2024Article
- Protective effects of GαNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Effects of Long-Term Administration of Bovine Bone Gelatin Peptides on Myocardial Hypertrophy in Spontaneously Hypertensive Rats.Nutrients · 2023Article
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- Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.Frontiers in cardiovascular medicine · 2023Review
- Mulberry (Life (Basel, Switzerland) · 2022Article
- Exercise training maintains cardiovascular health: signaling pathways involved and potential therapeutics.Signal transduction and targeted therapy · 2022Review
- Cardiac metabolic remodelling in chronic kidney disease.Nature reviews. Nephrology · 2022Review
- Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia-Reperfusion Injury in Diet-Induced Obesity.International journal of molecular sciences · 2022Article
- SIRPα Mediates IGF1 Receptor in Cardiomyopathy Induced by Chronic Kidney Disease.Circulation research · 2022Article
- Animal Models of Dysregulated Cardiac Metabolism.Circulation research · 2022Review
- Neu3 Sialidase Activates the RISK Cardioprotective Signaling Pathway during Ischemia and Reperfusion Injury (IRI).International journal of molecular sciences · 2022Article
- Role of Cardiac Fibroblasts in Cardiac Injury and Repair.Current cardiology reports · 2022Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issuedHemmings, Brian [corrected to Hemmings, Brian A]
Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
Acute activation of the serine-threonine kinase Akt is cardioprotective and reduces both infarction and dysfunction after ischemia/reperfusion injury (IRI). However, less is known about the chronic effects of Akt activation in the heart, and, paradoxically, Akt is activated in samples from patients with chronic heart failure. We generated Tg mice with cardiac-specific expression of either activated (myristoylated [myr]) or dominant-negative (dn) Akt and assessed their response to IRI in an ex vivo model. While dn-Akt hearts demonstrated a moderate reduction in functional recovery after IRI, no function was restored in any of the myr-Akt-Tg hearts. Moreover, infarcts were dramatically larger in myr-Akt-Tg hearts. Biochemical analyses demonstrated that chronic Akt activation induces feedback inhibition of PI3K activity through both proteasome-dependent degradation of insulin receptor substrate-1 (IRS-1) and inhibition of transcription of IRS-1 as well as that of IRS-2. To test the functional significance of these signaling changes, we performed in vivo cardiac gene transfer with constitutively active PI3K in myr-Akt-Tg mice. Restoration of PI3K rescued function and reduced injury after IRI. These data demonstrate that PI3K-dependent but Akt-independent effectors are required for full cardioprotection and suggest a mechanism by which chronic Akt activation can become maladaptive.
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What OpenQuestion holds
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.