ArticleThe Journal of clinical investigation2023
A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- PHLPP is neither a Phosphatase nor a Tumor Suppressor.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Discovery of a snail hibernation-inducer offering hibernation-like cardioprotection through metabolic rewiring and autophagy in mice.Nature communications · 2026Article
- Aberrant amino acid-sensing promotes immunotherapy resistance via the inflammatory cytokine-ZBTB5-mTORC1 axis.Nature cell biology · 2026Article
- Emergency preservation and resuscitation in exsanguination cardiac arrest: science fiction to future reality?Trauma surgery & acute care open · 2026Review
- The fuzzy MAD stroke conjecture, using Fuzzy C Means to classify multimodal apparent diffusion for ischemic stroke lesion stratification.Magnetic resonance imaging · 2025Article
- Phlpp1 alters the murine chondrocyte phospho-proteome during endochondral bone formation.Bone · 2024Article
- Noncanonical microprotein regulation of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity.Journal of the American Heart Association · 2024Article
- Thromboinflammation and the Role of Platelets.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Blockage of PHLPP1 protects against myocardial ischemia/reperfusion injury in diabetic mice via activation of STAT3 signaling.Journal of bioenergetics and biomembranes · 2023Article
- CPR: cardiac phosphatase in resuscitation.The Journal of clinical investigation · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
Out-of-hospital cardiac arrest is a leading cause of death in the US, with a mortality rate over 90%. Preclinical studies demonstrate that cooling during cardiopulmonary resuscitation (CPR) is highly beneficial, but can be challenging to implement clinically. No medications exist for improving long-term cardiac arrest survival. We have developed a 20-amino acid peptide, TAT-PHLPP9c, that mimics cooling protection by enhancing AKT activation via PH domain leucine-rich repeat phosphatase 1 (PHLPP1) inhibition. Complementary studies were conducted in mouse and swine. C57BL/6 mice were randomized into blinded saline control and peptide-treatment groups. Following a 12-minute asystolic arrest, TAT-PHLPP9c was administered intravenously during CPR and significantly improved the return of spontaneous circulation, mean arterial blood pressure and cerebral blood flow, cardiac and neurological function, and survival (4 hour and 5 day). It inhibited PHLPP-NHERF1 binding, enhanced AKT but not PKC phosphorylation, decreased pyruvate dehydrogenase phosphorylation and sorbitol production, and increased ATP generation in heart and brain. TAT-PHLPP9c treatment also reduced plasma taurine and glutamate concentrations after resuscitation. The protective benefit of TAT-PHLPP9c was validated in a swine cardiac arrest model of ventricular fibrillation. In conclusion, TAT-PHLPP9c may improve neurologically intact cardiac arrest survival without the need for physical cooling.
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Identifiers
What Socratic 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 Socratic graph.