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.
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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Myeloperoxidase aggravates pulmonary arterial hypertension by activation of vascular Rho-kinase
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AD Rieg, S Suleiman, C Anker, E Verjans, R Rossaint, S Uhlig, C Martin |
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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 |
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CJ Hu, H Zhang, A Laux, SS Pullamsetti, KR Stenmark |
The Journal of Physiology | 2018 |
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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 |