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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
Citation information
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Citations to this article in year 2013 (36)

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A comprehensive review: the evolution of animal models in pulmonary hypertension research; are we there yet?
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A Houssaini, S Abid, N Mouraret, F Wan, D Rideau, M Saker, E Marcos, CM Tissot, JL Dubois-Randé, V Amsellem, S Adnot
American journal of respiratory cell and molecular biology 2013
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M Izikki, O Mercier, F Lecerf, LL Guin, E Hoang, P Dorfmüller, F Perros, M Humbert, G Simonneau, P Dartevelle, E Fadel, S Eddahibi
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