ArticleAmerican journal of respiratory and critical care medicine2012
A critical role for p130Cas in the progression of pulmonary hypertension in humans and rodents.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Dasatinib induces lung vascular toxicity and predisposes to pulmonary hypertension.The Journal of clinical investigation · 2016Trial
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Emerging Gene Therapy Based on Nanocarriers: A Promising Therapeutic Alternative for Cardiovascular Diseases and a Novel Strategy in Valvular Heart Disease.International journal of molecular sciences · 2025Review
- Growth factors involved in vascular remodeling in pulmonary arterial hypertension.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2025Review
- The role of p130Cas/BCAR1 adaptor protein in the pathogenesis of cardiovascular diseases: A literature review.American heart journal plus : cardiology research and practice · 2024Review
- Receptor Tyrosine Kinase: Still an Interesting Target to Inhibit the Proliferation of Vascular Smooth Muscle Cells.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Biomarkers of haemodynamic severity of systemic sclerosis-associated pulmonary arterial hypertension by serum proteome analysis.Annals of the rheumatic diseases · 2023Article
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- Hypoxic pulmonary endothelial cells release epidermal growth factor leading to vascular smooth muscle cell arginase-2 expression and proliferation.Physiological reports · 2022Article
- Recent Developments in Nanomaterials-Based Drug Delivery and Upgrading Treatment of Cardiovascular Diseases.International journal of molecular sciences · 2022Review
- Metabolic reprogramming: A novel metabolic model for pulmonary hypertension.Frontiers in cardiovascular medicine · 2022Review
- Endothelial cells in the pathogenesis of pulmonary arterial hypertension.The European respiratory journal · 2021Review
- CDC2 Is an Important Driver of Vascular Smooth Muscle Cell Proliferation via FOXM1 and PLK1 in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2021Article
- Glutaminolysis: A Driver of Vascular and Cardiac Remodeling in Pulmonary Arterial Hypertension.Frontiers in cardiovascular medicine · 2021Review
- Article
- Joint Transcriptomic Analysis of Lung Cancer and Other Lung Diseases.Frontiers in genetics · 2019Article
- Macrophage Migration Inhibitory Factor (MIF) Inhibition in a Murine Model of Bleomycin-Induced Pulmonary Fibrosis.International journal of molecular sciences · 2018Article
- Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationalePulmonary arterial hypertension (PAH) is a progressive and fatal disease characterized by pulmonary arterial muscularization due to excessive pulmonary vascular cell proliferation and migration, a phenotype dependent upon growth factors and activation of receptor tyrosine kinases (RTKs). p130(Cas) is an adaptor protein involved in several cellular signaling pathways that control cell migration, proliferation, and survival.
objectivesWe hypothesized that in experimental and human PAH p130(Cas) signaling is overactivated, thereby facilitating the intracellular transmission of signal induced by fibroblast growth factor (FGF)2, epidermal growth factor (EGF), and platelet-derived growth factor (PDGF). MEASUREMENTS AND MAIN
resultsIn patients with PAH, levels of p130(Cas) protein and/or activity are higher in the serum, in the walls of distal pulmonary arteries, in cultured smooth muscle cells (PA-SMCs), and in pulmonary endothelial cells (P-ECs) than in control subjects. These abnormalities in the p130(Cas) signaling were also found in the chronically hypoxic mice and monocrotaline-injected rats as models of human PAH. We obtained evidence for the convergence and amplification of the growth-stimulating effect of the EGF-, FGF2-, and PDGF-signaling pathways via the p130(Cas) signaling pathway. We found that daily treatment with the EGF-R inhibitor gefitinib, the FGF-R inhibitor dovitinib, and the PDGF-R inhibitor imatinib started 2 weeks after a subcutaneous monocrotaline injection substantially attenuated the abnormal increase in p130(Cas) and ERK1/2 activation and regressed established pulmonary hypertension.
conclusionsOur findings demonstrate that p130(Cas) signaling plays a critical role in experimental and idiopathic PAH by modulating pulmonary vascular cell migration and proliferation and by acting as an amplifier of RTK downstream signals.
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