title: Imatinib mesylate  for the treatment of pulmonary arterial hypertension.
abstract: BACKGROUND
  Despite recent advances, pulmonary arterial hypertension (PAH) remains a devastating disease which harbors a poor prognosis. Novel therapeutic approaches directly targeting pulmonary vascular remodeling are warranted.
  
  
  METHODS
  This review delineates the current limitations in the management of PAH and focuses on a novel, anti-proliferative therapeutic concept. It will help readers understand the mechanisms of receptor tyrosine kinase signaling, with a special focus on platelet-derived growth factor (PDGF) receptors and their role in the pathobiology of PAH. Furthermore, it provides a comprehensive summary regarding the rationale, efficacy and safety of the tyrosine kinase inhibitor imatinib mesylate , which potently inhibits the PDGF receptor, as an additional treatment option in PAH.
  
  
  CONCLUSIONS
  PDGF is a potent mitogen for pulmonary vascular smooth muscle cells and represents an important mediator of pulmonary vascular remodeling. Imatinib mesylate, a compound that inhibits the Bcr-Abl kinase and was developed for the treatment of chronic myeloid leukemia, also targets PDGF receptors. Both experimental and clinical data indicate that it reverses the vascular remodeling process even when it is fully established. Results from Phase II and III clinical trials suggest potent and prolonged efficacy in patients with severe PAH (i.e., pulmonary vascular resistance > 800 dynes*s*cm(-5)). Future studies should evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, this compound is likely to become an additional treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.
authors.affiliation: Klinik III für Innere Medizin, Center for Molecular Medicine Cologne, Universität zu Köln, Kerpener Str. 62, 50924 Köln, Germany.
authors.forename: Henrik
authors.initials: H
authors.lastname: ten Freyhaus
authors.forename: Daniel
authors.initials: D
authors.lastname: Dumitrescu
authors.forename: Eva
authors.initials: E
authors.lastname: Berghausen
authors.forename: Marius
authors.initials: M
authors.lastname: Vantler
authors.forename: Evren
authors.initials: E
authors.lastname: Caglayan
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
mesh_terms: D000818:Animals; D001549:Benzamides; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000068877:Imatinib Mesylate; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor