ArticleAmerican journal of respiratory cell and molecular biology2013
Rapamycin reverses pulmonary artery smooth muscle cell proliferation in pulmonary hypertension.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers, 1 of them a synthesis that pooled it.
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Who cites it
89 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Evidence for PDZ-Binding Kinase in Lung Disease With an Emphasis on PAH.Pulmonary circulation · 2026Review
- Flavonoids: Potential New Drug Candidates for Attenuating Vascular Remodeling in Pulmonary Hypertension.International journal of molecular sciences · 2025Review
- Involvement of TGF-β, mTOR, and inflammatory mediators in aging alterations during myxomatous mitral valve disease in a canine model.GeroScience · 2025Review
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Cellular senescence in adult pulmonary hypertension: current state and future challenges.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- Transcriptional signatures of endothelial cells shape immune responses in cardiopulmonary health and disease.JCI insight · 2025Review
- Dysregulation of Mitochondrial in Pulmonary Hypertension-Related Right Ventricular Remodeling: Pathophysiological Features and Targeting Drugs.Reviews in cardiovascular medicine · 2025Review
- Chloroquine Restores eNOS Signaling in Shunt Endothelial Cells via Inhibiting eNOS Uncoupling.International journal of molecular sciences · 2025Article
- Molecular remodeling in comorbidities associated with heart failure: a current update.Molecular biology reports · 2024Review
- Cellular and Molecular Biology of Mitochondria in Chronic Obstructive Pulmonary Disease.International journal of molecular sciences · 2024Review
- Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. FromJournal of Cancer · 2024Article
- Cellular senescence in the pathogenesis of pulmonary arterial hypertension: the good, the bad and the uncertain.Frontiers in immunology · 2024Review
- Metallothionein 3 Potentiates Pulmonary Artery Smooth Muscle Cell Proliferation by Promoting Zinc-MTF1-ATG5 Axis-mediated Autophagosome Formation.International journal of biological sciences · 2024Article
- Current Management and Future Directions for Pulmonary Arterial Hypertension Associated with Congenital Heart Disease.Journal of personalized medicine · 2023Review
- Article
- Targeting Mitochondrial Metabolic Dysfunction in Pulmonary Hypertension: Toward New Therapeutic Approaches?International journal of molecular sciences · 2023Review
- PIF1 Promotes Autophagy to Inhibit Chronic Hypoxia Induced Apoptosis of Pulmonary Artery Endothelial Cells.International journal of chronic obstructive pulmonary disease · 2023Article
- Cross-talk between TSC2 and the extracellular matrix controls pulmonary vascular proliferation and pulmonary hypertension.Science signaling · 2022Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary artery (PA) smooth muscle cell (SMC) proliferation in pulmonary hypertension (PH) may be linked to dysregulated mammalian target of rapamycin (mTOR) signaling. The mTOR pathway involves two independent complexes, mTORC1 and mTORC2, which phosphorylate S6 kinase (S6K) and serine/threonine kinase (Akt), respectively, and differ in their sensitivity to rapamycin. Here, we evaluated rapamycin-sensitive mTOR substrates and PA-SMC proliferation in rats with monocrotaline (MCT)-induced PH (MCT-PH). Compared with cells from control rats, cultured PA-SMCs from MCT-PH rats exhibited increased growth responses to platelet-derived growth factor, serotonin (5-hydroxytryptophan), IL-1β, insulin-like growth factor-1, or fetal calf serum (FCS), with increases in phosphorylated (Ser-473)Akt, (Thr-308)Akt, glycogen synthase kinase (GSK)3, and S6K reflecting activated mTORC1 and mTORC2 signaling. Treatment with rapamycin (0.5 μM) or the Akt inhibitor, A-443654 (0.5 μM), reduced FCS-stimulated growth of PA-SMCs from MCT-PH rats to the level in control rats while inhibiting Akt, GSK3, and S6K activation. Neither the tyrosine kinase inhibitor, imatinib (0.1 μM), nor the 5-hydroxytryptophan transporter inhibitor, fluoxetine (5 μM), normalized the increased PA-SMC growth response to FCS. Rapamycin treatment (5 mg/kg/d) of MCT-PH rats from Day 21 to Day 28 markedly reduced phoshop (p)-Aky, p-GSK3, and p-S6K in PAs, and normalized growth of derived PA-SMCs. This effect was not observed after 1 week of imatinib (100 mg/kg/d) or fluoxetine (20 mg/kg/d). Rapamycin given preventively (Days 1-21) or curatively (Days 21-42) inhibited MCT-PH to a greater extent than did imatinib or fluoxetine. Experimental PH in rats is associated with a sustained proliferative PA-SMC phenotype linked to activation of both mTORC1 and mTORC2 signaling and is suppressed by rapamycin treatment.
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