ArticleThe Journal of clinical investigation2021
Disrupted PI3K subunit p110α signaling protects against pulmonary hypertension and reverses established disease in rodents.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- The Role of Piezo Ion Channels in Pulmonary Hypertension.Pulmonary circulation · 2026Review
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Mechanistic insights into the role of EGLN3 in pulmonary vascular remodeling and endothelial dysfunction.Respiratory research · 2025Review
- Endothelial PHD2 deficiency induces apoptosis resistance and inflammation via AKT activation and AIP1 loss independent of HIF2α.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension.EMBO molecular medicine · 2024Article
- Retinoblastoma: An update on genetic origin, classification, conventional to next-generation treatment strategies.Heliyon · 2024Review
- BMPR2 Loss Activates AKT by Disrupting DLL4/NOTCH1 and PPARγ Signaling in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Article
- Disruption of DLL4/NOTCH1 Causes Dysregulated PPARγ/AKT Signaling in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2024Article
- Cell Death in Pulmonary Arterial Hypertension.International journal of medical sciences · 2024Review
- Sex-biased TGFβ signalling in pulmonary arterial hypertension.Cardiovascular research · 2023Review
- Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension-Mechanisms and Mitigation.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Electrical Remodeling in Right Ventricular Failure Due to Pulmonary Hypertension: Unraveling Novel Therapeutic Targets.International journal of molecular sciences · 2023Article
- Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.Frontiers in immunology · 2023Review
- Role of Endothelin-1 in Right Atrial Arrhythmogenesis in Rabbits with Monocrotaline-Induced Pulmonary Arterial Hypertension.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
Enhanced signaling via RTKs in pulmonary hypertension (PH) impedes current treatment options because it perpetuates proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Here, we demonstrated hyperphosphorylation of multiple RTKs in diseased human vessels and increased activation of their common downstream effector phosphatidylinositol 3'-kinase (PI3K), which thus emerged as an attractive therapeutic target. Systematic characterization of class IA catalytic PI3K isoforms identified p110α as the key regulator of pathogenic signaling pathways and PASMC responses (proliferation, migration, survival) downstream of multiple RTKs. Smooth muscle cell-specific genetic ablation or pharmacological inhibition of p110α prevented onset and progression of pulmonary hypertension (PH) as well as right heart hypertrophy in vivo and even reversed established vascular remodeling and PH in various animal models. These effects were attributable to both inhibition of vascular proliferation and induction of apoptosis. Since this pathway is abundantly activated in human disease, p110α represents a central target in PH.
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Registered trials
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