Task: Question Generation
Input (English): Context: An abnormal ratio of vasohibin-2/vasohibin-1 may be involved in the abnormal angiogenesis and vascular remodeling during pulmonary arterial hypertension (PAH).', 'To evaluate the pharmacological actions of Ponatinib (AP) in experimental model of PAH, the effects of AP on TGF-β1-mediated endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMEC), and the hypoxic human pulmonary artery smooth muscle cells (HPASMC) proliferation and HPMEC in vitro, and on bleomycin (BLM)-induced PAH in vivo were investigated.', 'AP treatment resulted in a reduction of EndoMT in HPMECs with a decrease of vimentin, whereas an increase of VE-cadherin, reduction of fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and vasohibin-2 (VASH-2), whereas an increase of vasohibin-1 (VASH-1) in the hypoxic HPMEC, a reduction of the HPASMC proliferation with decreases of wnt5a, β-catenin and cyclin D1 expression. AP ameliorated BLM-induced PAH in rats with reductions of FGF-2, VEGF, von Willebrand factor (vWF) and VASH-2 expression, whereas an increase of VASH-1 expression. AP ameliorated BLM-induced PAH in rats with reductions of the pathological score and the collagen deposition. In addition, AP ameliorated hemodynamics and right ventricular hypertrophy.
Answer: Our results identified a therapeutic potential of AP in PAH therapy might be modulated VASH-2/VASH-1 and the Wnt signaling.
Output (English): Does ponatinib attenuate experimental pulmonary arterial hypertension by modulating Wnt signaling and vasohibin-2/vasohibin-1?