Imatinib in pulmonary arterial hypertension: c-Kit inhibition

Samar Farha, Raed Dweik, Franck Rahaghi, Raymond Benza, Paul Hassoun, Robert Frantz, Fernando Torres, Deborah A. Quinn, Suzy Comhair, Serpil Erzurum, Kewal Asosingh

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow-derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit+ hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit+ and CD34+CD133+ hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34+ CD133+ and c-Kit+ progenitor cells as well as c-Kit+/CD34+CD133+ decreased with imatinib therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism ofaction ofimatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy.

Original languageEnglish (US)
Pages (from-to)452-455
Number of pages4
JournalPulmonary Circulation
Issue number3
StatePublished - Sep 2014


  • Imatinib
  • Mast cells
  • Progenitor cells
  • Pulmonary hypertension
  • c-Kit

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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