title: Protein Expression by Human Pulmonary Artery Smooth Muscle Cells Containing aBMPR2Mutation and the Action of ET-1 as Determined by Proteomic Mass Spectrometry.
abstract: 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.
authors: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 USA.
authors: Chunxiang
authors: C
authors: Yao
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 USA.
authors: Jun
authors: J
authors: Yu
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 USA.
authors: Linda
authors: L
authors: Taylor
authors: Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 USA.
authors: Peter
authors: P
authors: Polgar
authors: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 USA.
authors: Mark E
authors: ME
authors: McComb
authors: Center for Biomedical Mass Spectrometry, Boston University School of Medicine, 670 Albany St., Boston, MA 02118 USA ; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118 USA.
authors: Catherine E
authors: CE
authors: Costello
keywords: BMPR2; endothelin-1; label-free quantitation; proteomic mass spectrometry; pulmonary arterial hypertension; signal transduction