ArticleAmerican journal of respiratory cell and molecular biology2017
Pharmacological Inhibition of mTOR Kinase Reverses Right Ventricle Remodeling and Improves Right Ventricle Structure and Function in Rats.
Article in American journal of respiratory cell and molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Canonical and emerging regulatory mechanisms of tissue remodeling: shared principles across organs and therapeutic opportunities.Frontiers in immunology · 2026Review
- The effects of sodium-glucose cotransporter 2 inhibitors on the 'forgotten' right ventricle.ESC heart failure · 2025Review
- Dysregulation of Mitochondrial in Pulmonary Hypertension-Related Right Ventricular Remodeling: Pathophysiological Features and Targeting Drugs.Reviews in cardiovascular medicine · 2025Review
- Deciphering the inhibitory effects of trimetazidine on pulmonary hypertension development via decreasing fatty acid oxidation and promoting glucose oxidation.Scientific reports · 2024Article
- Exploring the impact of circRNAs on cancer glycolysis: Insights into tumor progression and therapeutic strategies.Non-coding RNA research · 2024Review
- Article
- Pulmonary Hypertension and Right Ventricle: A Pathophysiological Insight.Clinical Medicine Insights. Cardiology · 2024Review
- Hyperactive mTORC1 in lung mesenchyme induces endothelial cell dysfunction and pulmonary vascular remodeling.The Journal of clinical investigation · 2023Article
- E-cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in Pulmonary Arterial Hypertension.Stem cells (Dayton, Ohio) · 2023Article
- Cross-talk between TSC2 and the extracellular matrix controls pulmonary vascular proliferation and pulmonary hypertension.Science signaling · 2022Article
- Noncanonical HIPPO/MST Signaling via BUB3 and FOXO Drives Pulmonary Vascular Cell Growth and Survival.Circulation research · 2022Article
- A wrinkle in time: circadian biology in pulmonary vascular health and disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Differential Expression Profile of microRNAs and Tight Junction in the Lung Tissues of Rat With Mitomycin-C-Induced Pulmonary Veno-Occlusive Disease.Frontiers in cardiovascular medicine · 2022Article
- Article
- Novel Therapeutic Targets for the Treatment of Right Ventricular Remodeling: Insights from the Pulmonary Artery Banding Model.International journal of environmental research and public health · 2021Review
- Inhibition of mTOR by rapamycin does not improve hypoxic pulmonary hypertension-induced right heart failure in old mice.Experimental gerontology · 2021Article
- Oxygen sensing, mitochondrial biology and experimental therapeutics for pulmonary hypertension and cancer.Free radical biology & medicine · 2021Article
- Review
- mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.International journal of molecular sciences · 2021Review
- Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling.American journal of respiratory and critical care medicine · 2020Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased pulmonary artery (PA) pressure, right-heart afterload and death. Mechanistic target of rapamycin (mTOR) promotes smooth muscle cell proliferation, survival, and pulmonary vascular remodeling via two functionally distinct mTOR complexes (mTORCs)-1 (supports cell growth) and -2 (promotes cell survival), and dual mTORC1/mTORC2 inhibition selectively induces pulmonary arterial hypertension PA vascular smooth muscle cell apoptosis and reverses pulmonary vascular remodeling. The consequences of mTOR inhibition on right ventricle (RV) morphology and function are not known. Using SU5416/hypoxia rat model of pulmonary hypertension (PH), we report that, in contrast to activation of both mTORC1 and mTORC2 pathways in small remodeled PAs, RV tissues had predominant up-regulation of mTORC1 signaling accompanied by cardiomyocyte and RV hypertrophy, increased RV wall thickness, RV/left ventricle end-diastolic area ratio, RV contractility and afterload (arterial elastance), and shorter RV acceleration time compared with controls. Treatment with mTOR kinase inhibitor, PP242, at Weeks 6-8 after PH induction suppressed both mTORC1 and mTORC2 in small PAs, but only mTORC1 signaling in RV, preserving basal mTORC2-Akt levels. Vehicle-treated rats showed further PH and RV worsening and profound RV fibrosis. PP242 reversed pulmonary vascular remodeling and prevented neointimal occlusion of small PAs, significantly reduced PA pressure and pulmonary vascular resistance, reversed cardiomyocyte hypertrophy and RV remodeling, improved max RV contractility, arterial elastance, and RV acceleration time, and prevented development of RV fibrosis. Collectively, these data show a predominant role of mTORC1 versus mTORC2 in RV pathology, and suggest potential attractiveness of mTOR inhibition to simultaneously target pulmonary vascular remodeling and RV dysfunction in established PH.
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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.