Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension.

ABSTRACT: Pulmonary hypertension (PH) and cancer pathology share growth factor- and MAPK stress-mediated signaling pathways resulting in endothelial and smooth muscle cell dysfunction and angioproliferative vasculopathy. In this study, we assessed sorafenib, an antineoplastic agent and inhibitor of multiple kinases important in angiogenesis [VEGF receptor (VEGFR)-1-3, PDGF receptor (PDGFR)-beta, Raf-1 kinase] as a potential PH therapy. Two PH rat models were used: a conventional hypoxia-induced PH model and an augmented PH model combining dual VEGFR-1 and -2 inhibition (SU-5416, single 20 mg/kg injection) with hypoxia. In addition to normoxia-exposed control animals, four groups were maintained at 10% inspired O(2) fraction for 3.5 wk (hypoxia/vehicle, hypoxia/SU-5416, hypoxia/sorafenib, and hypoxia

SUBMITTER: Moreno-Vinasco L 

PROVIDER: S-EPMC3616402 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature