Imatinib mesylate has the potential to exert its efficacy by down-regulating the plasma concentration of platelet-derived growth factor in patients with pulmonary arterial hypertension

Int Heart J. 2010 Jul;51(4):272-6. doi: 10.1536/ihj.51.272.


Recently, platelet-derived growth factor (PDGF) has been implicated in the abnormal proliferation and migration of pulmonary artery vascular smooth muscle cells. Imatinib meslylate, a PDGF receptor antagonist, has been reported to dramatically improve pulmonary arterial hypertension (PAH) in some human cases as well as animal models. Five patients with PAH (3 scleroderma-associated PAH and 2 idiopathic/familial PAH) taking no less than 2 PAH agents were treated with low-dose imatinib (100 mg/day) for 24 weeks. Imatinib was titrated up to 200 mg/day unless major complications were observed. Before and after the treatment, right heart catheterization, cardiopulmonary exercise test, respiratory function test, and plasma concentration measurements of PDGF-BB and vascular endothelial growth factor (VEGF) were performed. Plasma PDGF-BB levels were significantly decreased after 12 weeks of treatment (P = 0.04), while VEGF did not change. Although 24 week administration of imatinib did not show a significant effect on hemodynamics and exercise capacity, 2 patients with high plasma PDGF-BB levels showed a good initial response of more than a 15% decrease in pulmonary vascular resistance. Diffusion capacity of the lung for carbon monoxide significantly improved after 12 weeks of treatment (P < 0.01) and this improvement tended to be sustained for 24 weeks (P = 0.05). Renal dysfunction was observed in 3 patients during imatinib therapy. The upregulated PDGF-BB in patients with PAH could be suppressed by imatinib treatment, and also seemed to be one of the determinant factors for its efficacy.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Becaplermin
  • Benzamides
  • Cardiac Output
  • Cohort Studies
  • Exercise Tolerance
  • Female
  • Humans
  • Hypertension, Pulmonary / blood*
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Platelet-Derived Growth Factor / metabolism*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-sis
  • Pyrimidines / therapeutic use*
  • Treatment Outcome
  • Vascular Resistance
  • Young Adult


  • Benzamides
  • Piperazines
  • Platelet-Derived Growth Factor
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-sis
  • Pyrimidines
  • Becaplermin
  • Imatinib Mesylate