• Int Heart J · Jul 2010

    Clinical Trial

    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.

    • Masaru Hatano, Atsushi Yao, Taro Shiga, Koichiro Kinugawa, Yasunobu Hirata, and Ryozo Nagai.
    • Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan.
    • Int Heart J. 2010 Jul 1;51(4):272-6.

    AbstractRecently, 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.

      Pubmed     Free full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        

    hide…