Pulmonary pressure reduction attenuates expression of proteins identified by lung proteomic profiling in pulmonary hypertensive rats
Autor: | Britt Elmedal Laursen, Henrik Vorum, Bent Honoré, Michael J. Mulvany, Ulf Simonsen, Jonas Baandrup, Lise Bech Thorsen, Louise Østergaard, Yvonne Eskildsen-Helmond |
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Rok vydání: | 2011 |
Předmět: |
Male
Proteomics Proteome Pyridines Hypertension Pulmonary Molecular Sequence Data Cathepsin D Biology Pharmacology Biochemistry Piperazines Sildenafil Citrate Annexin medicine Animals Amino Acid Sequence Sulfones Translation factor Rats Wistar Hypoxia Lung Molecular Biology Activator (genetics) Hemodynamics Phosphodiesterase 5 Inhibitors Hypoxia (medical) medicine.disease Pulmonary hypertension Rats medicine.anatomical_structure Gene Expression Regulation Guanylate Cyclase Purines Immunology Pyrazoles medicine.symptom Soluble guanylyl cyclase Signal Transduction |
Zdroj: | Østergaard, L, Honoré, B, Thorsen, L B, Baandrup, J, Eskildsen-Helmond, Y, Laursen, B E, Vorum, H, Mulvany, M J & Simonsen, U 2011, ' Pulmonary pressure reduction attenuates expression of proteins identified by lung proteomic profiling in pulmonary hypertensive rats ', Proteomics, vol. 11, no. 23, pp. 4492-502 . https://doi.org/10.1002/pmic.201100171 |
ISSN: | 1615-9853 |
DOI: | 10.1002/pmic.201100171 |
Popis: | 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. |
Databáze: | OpenAIRE |
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