International Heart Journal
Online ISSN : 1349-3299
Print ISSN : 1349-2365
ISSN-L : 1349-2365
Clinical Studies
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 HatanoAtsushi YaoTaro ShigaKoichiro KinugawaYasunobu HirataRyozo Nagai
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2010 Volume 51 Issue 4 Pages 272-276

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Abstract

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.

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© 2010 by the International Heart Journal Association
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