Protein expression by human pulmonary artery smooth muscle cells containing a BMPR2 mutation and the action of ET-1 as determined by proteomic mass spectrometry

•Pulmonary arterial hypertension (PAH) increases vascular resistance and smooth muscle cells.•Endothelin-1 (ET-1), a potent vasoconstrictor, is linked to etiology and progression of PAH.•Proteomic mass spectrometry reveals PAH pathway changes and ET-1 effects.•PAH increases multiple signaling and protein degradation pathways; enhances response to ET-1.•Bone morphogenetic protein type II receptor (BMPR2) mutation likely affects PAH pathology.

Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and remodeling. Increase in the population of vascular smooth muscle cells is among the key events contributing to the remodeling. Endothelin-1 (ET-1), a potent vasoconstrictor, is linked to the etiology and progression of PAH. Here we analyze changes in protein expressions in response to ET-1 in pulmonary arterial smooth muscle cells (PASMC) from a healthy Control (non-PAH) and a PAH subject presenting a bone morphogenetic protein type II receptor (BMPR2) mutation with exon 1–8 deletion. Protein expressions were analyzed by proteomic mass spectrometry using label-free quantitation and the correlations were subjected to Ingenuity™ Pathway Analysis. The results point to eIF2/mTOR/p70S6K, RhoA/actin cytoskeleton/integrin and protein unbiquitination as canonical pathways whose protein expressions increase with the development of PAH. These pathways have an intimal function in the PAH-related physiology of smooth muscle proliferation, apoptosis, contraction and cellular stress. Exposure of the cells to ET-1 further increases protein expression within these pathways. Thus our results show changes in signaling pathways as a consequence of PAH and the effect of ET-1 interference on Control and PAH-affected cells.

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