Triple-tyrosine kinase inhibition attenuates pulmonary arterial hypertension and neointimal formation

Translational Research : the Journal of Laboratory and Clinical Medicine
Anjira S AmbadeDongmei Wu

Abstract

The present study examined the effects of simultaneous inhibition of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptor signaling with BIBF1000, a novel triple tyrosine kinase inhibitor on preventing and reversing the progression of severe pulmonary arterial hypertension (PAH) in an experimental model in rats. Left pneumonectomized male Wistar rats were injected with monocrotaline to induce PAH. Treatment with BIBF1000 from day 1 to day 21 after monocrotaline injection attenuated PAH development, as evidenced by lower values for pulmonary artery pressure (mPAP), right ventricular pressure (RVSP), pulmonary arterial neointimal formation, and the ratio of right ventricular weight to left ventricular and septum weight [RV/(LV+S)] on day 21 compared to control rats. Treatment with BIBF1000 from day 21 to day 42 after monocrotaline injection reversed established PAH as shown by normalized values for mPAP and RVSP, RV/(LV+S) ratio, pulmonary arterial occlusion scores, levels of heart and lung fibrosis, as well as improved survival. Treatment with BIBF1000 reduced inflammatory cell recruitment in bronchoalveolar lavage and lung tissues, reduced CD-68 positive ma...Continue Reading

Citations

May 7, 2021·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Aya YamamuraMotohiko Sato

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