Key result
BAY 412272 and sildenafil prevent hypoxia-induced pulmonary vascular remodeling and RV systolic pressure increases in rats.
Why the study?
Protein expression changes and novel signaling pathways in lungs from pulmonary hypertensive rats were not fully characterized.
Does BAY 412272 or sildenafil reduce right ventricular systolic pressure and alter protein expression in hypoxic rats with pulmonary hypertension?
Does BAY 412272 or sildenafil reduce right ventricular systolic pressure and alter protein expression in hypoxic rats with pulmonary hypertension?
Pulmonary pressure reduction with sildenafil or BAY 412272 attenuates hypoxia-induced protein expression and vascular muscularization in a rat model of pulmonary hypertension.
May identify treatment-responsive proteins in experimental PH; leaves open translation to human biomarkers or therapies.
The present study was designed to analyze protein expression in lungs from pulmonary hypertensive rats in order to identify novel signaling pathways. This was achieved by proteomic studies in which proteins from lung homogenates from hypoxic were compared to normoxic rats. The expression of these proteins was then investigated in lungs from hypoxic rats treated with either an activator of soluble guanylyl cyclase, BAY 412272, or an inhibitor of phosphodiesterase type 5, sildenafil. The proteomic study revealed an up-regulation of guanine nucleotide-binding protein β, GST-ω-1, cathepsin D, chloride intracellular channel subunit 5, annexin A4, F-actin capping protein CapZ (CapZα), and the translation factor elongation factor 1 δ in lungs from chronic hypoxic rats with pulmonary hypertension. Immunohistochemistry revealed that CapZα, cathepsin D, and annexin A4 were expressed in the pulmonary vascular wall and immunoblotting showed these proteins correlated to alterations in muscularization. Both drugs inhibited hypoxia-induced increase in right ventricular systolic pressure and pulmonary arterial muscularization, and prevented most of the protein regulations observed after hypoxia. These findings suggest that pulmonary pressure is an important factor for initiating signaling pathways leading to protein expression and muscularization in the pulmonary vasculature.
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Østergaard et al. (2011) studied Pulmonary hypertension. BAY 412272 or sildenafil vs. Untreated hypoxic rats was evaluated on Protein expression, right ventricular systolic pressure, and pulmonary arterial muscularization. Treatment with BAY 412272 or sildenafil inhibited hypoxia-induced increases in right ventricular systolic pressure and pulmonary arterial muscularization in rats, preventing most protein regulations.
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