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Citations to this article

Reversal of experimental pulmonary hypertension by PDGF inhibition
Ralph Theo Schermuly, … , Werner Seeger, Friedrich Grimminger
Ralph Theo Schermuly, … , Werner Seeger, Friedrich Grimminger
Published October 3, 2005
Citation Information: J Clin Invest. 2005;115(10):2811-2821. https://doi.org/10.1172/JCI24838.
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Research Article Vascular biology Article has an altmetric score of 18

Reversal of experimental pulmonary hypertension by PDGF inhibition

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Abstract

Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the disease. A 2-week treatment resulted in 100% survival, compared with only 50% in sham-treated rats. The changes in RV pressure, measured continuously by telemetry, and right heart hypertrophy were reversed to near-normal levels. STI571 prevented phosphorylation of the PDGF receptor and suppressed activation of downstream signaling pathways. Similar results were obtained in chronically hypoxic mice, which were treated with STI571 after full establishment of pulmonary hypertension. Moreover, expression of the PDGF receptor was found to be significantly increased in lung tissue from pulmonary arterial hypertension patients compared with healthy donor lung tissue. We conclude that STI571 reverses vascular remodeling and cor pulmonale in severe experimental pulmonary hypertension regardless of the initiating stimulus. This regimen offers a unique novel approach for antiremodeling therapy in progressed pulmonary hypertension.

Authors

Ralph Theo Schermuly, Eva Dony, Hossein Ardeschir Ghofrani, Soni Pullamsetti, Rajkumar Savai, Markus Roth, Akylbek Sydykov, Ying Ju Lai, Norbert Weissmann, Werner Seeger, Friedrich Grimminger

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Total
Citations: 8 16 11 20 25 23 21 16 22 17 16 28 36 26 32 26 20 14 6 5 1 389
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Citations to this article in year 2018 (16)

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JCI Insight 2018
PDGF-BB regulates the pulmonary vascular tone: impact of prostaglandins, calcium, MAPK- and PI3K/AKT/mTOR signalling and actin polymerisation in pulmonary veins of guinea pigs
AD Rieg, S Suleiman, C Anker, E Verjans, R Rossaint, S Uhlig, C Martin
Respiratory Research 2018
Sex differences in pulmonary arterial hypertension: role of infection and autoimmunity in the pathogenesis of disease
KA Batton, CO Austin, KA Bruno, CD Burger, BP Shapiro, DL Fairweather
Biology of sex differences 2018
Aryl Hydrocarbon Receptor Nuclear Translocator in Vascular Smooth Muscle Cells Is Required for Optimal Peripheral Perfusion Recovery
AH Borton, BL Benson, LE Neilson, A Saunders, MA Alaiti, AY Huang, MK Jain, A Proweller, DL RamirezBergeron
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2018
Recent advances in pulmonary arterial hypertension
MR Wilkins, J Aman, L Harbaum, A Ulrich, J Wharton, CJ Rhodes
F1000Research 2018
Mechanisms contributing to persistently activated cell phenotypes in pulmonary hypertension: Mechanisms responsible for persistent pulmonary hypertension
CJ Hu, H Zhang, A Laux, SS Pullamsetti, KR Stenmark
The Journal of Physiology 2018
Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both
JD Marshall, I Bazan, Y Zhang, WH Fares, PJ Lee
American journal of physiology. Lung cellular and molecular physiology 2018
Inhibition of Shp2 ameliorates monocrotaline-induced pulmonary arterial hypertension in rats
Y Cheng, M Yu, J Xu, M He, H Wang, H Kong, W Xie
BMC Pulmonary Medicine 2018
Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective
G Varricchi, P Ameri, C Cadeddu, A Ghigo, R Madonna, G Marone, V Mercurio, I Monte, G Novo, P Parrella, F Pirozzi, A Pecoraro, P Spallarossa, C Zito, G Mercuro, P Pagliaro, CG Tocchetti
Frontiers in physiology 2018
Polymorphonuclear Leukocytes in Pulmonary Hypertension and Fibrosis: Not Always What They Appear to Be
N Durmus, G Grunig
American journal of respiratory cell and molecular biology 2018
Reversal of the Warburg effect with DCA in PDGF‑treated human PASMC is potentiated by pyruvate dehydrogenase kinase‑1 inhibition mediated through blocking Akt/GSK‑3β signalling
B Li, Y Zhu, Q Sun, C Yu, L Chen, Y Tian, J Yan
International journal of molecular medicine 2018
Cerivastatin Nanoliposome as a Potential Disease Modifying Approach for the Treatment of Pulmonary Arterial Hypertension
Y Lee, SB Pai, RV Bellamkonda, DH Thompson, J Singh
The Journal of pharmacology and experimental therapeutics 2018
Epigenetic Dysregulation of the Dynamin-Related Protein 1 Binding Partners MiD49 and MiD51 Increases Mitotic Mitochondrial Fission and Promotes Pulmonary Arterial Hypertension: Mechanistic and Therapeutic Implications
KH Chen, A Dasgupta, J Lin, F Potus, S Bonnet, J Iremonger, J Fu, J Mewburn, D Wu, K Dunham-Snary, AL Theilmann, ZC Jing, C Hindmarch, ML Ormiston, A Lawrie, SL Archer
Circulation 2018
Inhibitory Antibodies against Activin A and TGF-β Reduce Self-Supported, but Not Soluble Factors-Induced Growth of Human Pulmonary Arterial Vascular Smooth Muscle Cells in Pulmonary Arterial Hypertension
T Kudryashova, Y Shen, A Pena, E Cronin, E Okorie, D Goncharov, E Goncharova
International journal of molecular sciences 2018
Imatinib for right heart failure in COPD
P Douschan, G Kovacs, V Foris, M Kuehnelt-Leddihn, H Olschewski
Pulmonary circulation 2018
Resolution of sickle cell disease–associated inflammation and tissue damage with 17 R -resolvin D1
A Matte, A Recchiuti, E Federti, B Koehl, T Mintz, WE Nemer, PL Tharaux, V Brousse, I Andolfo, A Lamolinara, O Weinberg, A Siciliano, PC Norris, IR Riley, A Iolascon, CN Serhan, C Brugnara, LD Franceschi
Blood 2018

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