ArticleCardiovascular research2017
Tipifarnib prevents development of hypoxia-induced pulmonary hypertension.
Article in Cardiovascular research, 2017. 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.
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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.
- Plasmodium-induced disruption of brain endothelial barrier integrity in vitro and in mice is prevented by inhibitors of farnesyltransferase.Malaria journal · 2026Article
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Hypoxic Pulmonary Hypertension: Molecular Mechanisms and Clinical Research Advances.International journal of molecular sciences · 2026Review
- Farnesyltransferase inhibitor LB42708 disables oncogenic RAS signaling and overcomes gefitinib resistance in NSCLC via FTase α-subunit and RAS degradation.Cell communication and signaling : CCS · 2026Article
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Novel hub genes associated with pulmonary artery remodeling in pulmonary hypertension.Frontiers in cardiovascular medicine · 2022Article
- Identifying Potential Mitochondrial Proteome Signatures Associated with the Pathogenesis of Pulmonary Arterial Hypertension in the Rat Model.Oxidative medicine and cellular longevity · 2022Article
- Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells.Journal of clinical medicine · 2021Article
- Review
- Single-Cell Study of Two Rat Models of Pulmonary Arterial Hypertension Reveals Connections to Human Pathobiology and Drug Repositioning.American journal of respiratory and critical care medicine · 2021Article
- Effects of Post-translational Modifications on Membrane Localization and Signaling of Prostanoid GPCR-G Protein Complexes and the Role of Hypoxia.The Journal of membrane biology · 2019Review
- FBXW7 regulates endothelial barrier function by suppression of the cholesterol synthesis pathway and prenylation of RhoB.Molecular biology of the cell · 2019Article
- Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension.The Journal of physiology · 2019Review
- Insights on the epigenetic mechanisms underlying pulmonary arterial hypertension.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018Review
- miR-190a-5p participates in the regulation of hypoxia-induced pulmonary hypertension by targeting KLF15 and can serve as a biomarker of diagnosis and prognosis in chronic obstructive pulmonary disease complicated with pulmonary hypertension.International journal of chronic obstructive pulmonary diseaseObservational
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
Aims: RhoB plays a key role in the pathogenesis of hypoxia-induced pulmonary hypertension. Farnesylated RhoB promotes growth responses in cancer cells and we investigated whether inhibition of protein farnesylation will have a protective effect. Methods and results: The analysis of lung tissues from rodent models and pulmonary hypertensive patients showed increased levels of protein farnesylation. Oral farnesyltransferase inhibitor tipifarnib prevented development of hypoxia-induced pulmonary hypertension in mice. Tipifarnib reduced hypoxia-induced vascular cell proliferation, increased endothelium-dependent vasodilatation and reduced vasoconstriction of intrapulmonary arteries without affecting cell viability. Protective effects of tipifarnib were associated with inhibition of Ras and RhoB, actin depolymerization and increased eNOS expression in vitro and in vivo. Farnesylated-only RhoB (F-RhoB) increased proliferative responses in cultured pulmonary vascular cells, mimicking the effects of hypoxia, while both geranylgeranylated-only RhoB (GG-RhoB), and tipifarnib had an inhibitory effect. Label-free proteomics linked F-RhoB with cell survival, activation of cell cycle and mitochondrial biogenesis. Hypoxia increased and tipifarnib reduced the levels of F-RhoB-regulated proteins in the lung, reinforcing the importance of RhoB as a signalling mediator. Unlike simvastatin, tipifarnib did not increase the expression levels of Rho proteins. Conclusions: Our study demonstrates the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension.
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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 OpenQuestion graph.