title: Treatment with platelet-derived growth factor (PDGF) and rock inhibitors is related to declined nerve growth factor (NGF) signaling in an experimental model of rat pulmonary hypertension.
abstract: BACKGROUND
  Recent studies reveal that nerve growth factor (NGF) plays a critical role in the pathobiology of pulmonary hypertension (PH). The aim of the present study is to clarify the relationship between NGF signaling and treatment with PDGF or ROCK inhibitors in an animal model of PH.
  
  
  METHODS
  Lung tissues were obtained from animals with monocrotaline (MCT)-challenged PH which had been administered long term imatinib, fasudil or statin. Reversal of disease was indicated by decreases in right ventricle pressure (RVP) and hypertrophy. NGF expression was examined at the mRNA and protein levels using quantitative real-time PCR reaction and ELISA.
  
  
  RESULTS
  MCT significantly increased NGF mRNA and protein content in lung tissue. ROCK inhibitor (fasudil) and PDGF inhibitor (imatinib) caused significant decreases in NGF mRNA and protein content when administered alone, with no further effects noted when used in combination.
  
  
  CONCLUSIONS
  The beneficial reversal of MCT-mediated effects in PH caused by PDGF or ROCK inhibition may be also partially mediated by decreased NGF signaling.
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland. Electronic address: magdalena.jasinska-stroschein@umed.lodz.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jasińska-Stroschein
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Łódź, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Oszajca
authors.affiliation: Department of Medical Biochemistry, Medical University of Łódź, Łódź, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Świtlik
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Ruchwa
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Orszulak-Michalak
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000068877:Imatinib Mesylate / Q000494:pharmacology; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016686:Monocrotaline; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000068877:Imatinib Mesylate; D020932:Nerve Growth Factor; D054460:rho-Associated Kinases; C049347:fasudil
keywords: Nerve growth factor; Platelet-derived growth factor; Pulmonary hypertension; Rat; RhoA kinase