title: Pulmonary pressure reduction attenuates expression of proteins identified by lung proteomic profiling in pulmonary hypertensive rats.
abstract: 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.
authors: Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
authors: Louise
authors: L
authors: Østergaard
authors: Bent
authors: B
authors: Honoré
authors: Lise B
authors: LB
authors: Thorsen
authors: Jonas
authors: J
authors: Baandrup
authors: Yvonne
authors: Y
authors: Eskildsen-Helmond
authors: Britt E
authors: BE
authors: Laursen
authors: Henrik
authors: H
authors: Vorum
authors: Michael J
authors: MJ
authors: Mulvany
authors: Ulf
authors: U
authors: Simonsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D006162:Guanylate Cyclase / Q000378:metabolism; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D020543:Proteome / Q000032:analysis* / Q000235:genetics* / Q000378:metabolism; D040901:Proteomics; D011687:Purines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D020543:Proteome; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; D013450:Sulfones; D000068677:Sildenafil Citrate; D006162:Guanylate Cyclase