ArticleJournal of the American Heart Association2019
PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.
Article in Journal of the American Heart Association, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 20 citations in OpenAlex.
- Morroniside Attenuates Doxorubicin-Induced Cardiotoxicity by Activating the PI3K/AKT/Nrf2/HO-1 Pathway to Inhibit Ferroptosis and Oxidative Stress.Journal of biochemical and molecular toxicology · 2026Article
- Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Review
- Unveiling the Complexities: Exploring Mechanisms of Anthracyclineinduced Cardiotoxicity.Current cardiology reviews · 2025Review
- NADPH oxidase 2 mediates cardiac sympathetic denervation and myocyte autophagy, resulting in cardiac atrophy and dysfunction in doxorubicin-induced cardiomyopathy.Scientific reports · 2024Article
- Protective effect of coenzyme Q10 against doxorubicin-induced cardiotoxicity: Scoping review article.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Pyridoxamine Limits Cardiac Dysfunction in a Rat Model of Doxorubicin-Induced Cardiotoxicity.Antioxidants (Basel, Switzerland) · 2024Article
- Loss of PI3Kα Mediates Protection From Myocardial Ischemia-Reperfusion Injury Linked to Preserved Mitochondrial Function.Journal of the American Heart Association · 2023Article
- COX5A Alleviates Doxorubicin-Induced Cardiotoxicity by Suppressing Oxidative Stress, Mitochondrial Dysfunction and Cardiomyocyte Apoptosis.International journal of molecular sciences · 2023Article
- [Honokiol reduces doxorubicin-induced cardiotoxicityNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Cardiomyocyte Atrophy, an Underestimated Contributor in Doxorubicin-Induced Cardiotoxicity.Frontiers in cardiovascular medicine · 2022Review
- Exploring the Pharmacological Mechanisms ofBioMed research international · 2021Article
- Cardiac Safety of Kinase Inhibitors - Improving Understanding and Prediction of Liabilities in Drug Discovery Using Human Stem Cell-Derived Models.Frontiers in cardiovascular medicine · 2021Article
- PI3K inhibitors in thrombosis and cardiovascular disease.Clinical and translational medicine · 2020Review
- PI3Kα in cardioprotection: Cytoskeleton, late NaChannels (Austin, Tex.) · 2019Review
- PI3Kα Pathway Inhibition With Doxorubicin Treatment Results in Distinct Biventricular Atrophy and Remodeling With Right Ventricular Dysfunction.Journal of the American Heart Association · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Background Cancer therapies inhibiting PI 3Kα (phosphoinositide 3-kinase-α)-dependent growth factor signaling, including trastuzumab inhibition of HER 2 (Human Epidermal Growth Factor Receptor 2), can cause adverse effects on the heart. Direct inhibition of PI 3Kα is now in clinical trials, but the effects of PI 3Kα pathway inhibition on heart atrophy, remodeling, and function in the context of cancer therapy are not well understood. Method and Results Pharmacological PI 3Kα inhibition and heart-specific genetic deletion of p110α, the catalytic subunit of PI 3Kα, was characterized in conjunction with anthracycline (doxorubicin) treatment in female murine models. Biventricular changes in heart morphological characteristics and function were analyzed, with molecular characterization of signaling pathways. Both PI 3Kα inhibition and anthracycline therapy promoted heart atrophy and a combined effect of distinct right ventricular dilation, dysfunction, and cardiomyocyte remodeling in the absence of pulmonary arterial hypertension. Congruent findings of right ventricular dilation and dysfunction were seen with pharmacological and genetic suppression of PI 3Kα signaling when combined with doxorubicin treatment. Increased p38 mitogen-activated protein kinase activation was mechanistically linked to heart atrophy and correlated with right ventricular dysfunction in explanted failing human hearts. Conclusions PI 3Kα pathway inhibition promotes heart atrophy in mice. The right ventricle is specifically at risk for dilation and dysfunction in the setting of PI 3K inhibition in conjunction with chemotherapy. Inhibition of p38 mitogen-activated protein kinase is a proposed therapeutic target to minimize this mode of cardiotoxicity.
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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 Socratic graph.