@prefix this: <http://www.tkuhn.ch/bel2nanopub/RAy36brDuhTMLs_7b2PkKe1lMBkVYMwtud5ktZDl29jjI> .
@prefix sub: <http://www.tkuhn.ch/bel2nanopub/RAy36brDuhTMLs_7b2PkKe1lMBkVYMwtud5ktZDl29jjI#> .
@prefix beldoc: <http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel> .
@prefix rdfs: <http://www.w3.org/2000/01/rdf-schema#> .
@prefix rdf: <http://www.w3.org/1999/02/22-rdf-syntax-ns#> .
@prefix xsd: <http://www.w3.org/2001/XMLSchema#> .
@prefix dct: <http://purl.org/dc/terms/> .
@prefix dce: <http://purl.org/dc/elements/1.1/> .
@prefix pav: <http://purl.org/pav/> .
@prefix np: <http://www.nanopub.org/nschema#> .
@prefix belv: <http://www.selventa.com/vocabulary/> .
@prefix prov: <http://www.w3.org/ns/prov#> .
@prefix chebi: <http://www.ebi.ac.uk/chebi/searchId.do?chebiId=> .
@prefix Protein: <http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_36080> .
@prefix entrez: <http://www.ncbi.nlm.nih.gov/gene/> .
@prefix geneProductOf: <http://purl.obolibrary.org/obo/RO_0002204> .
@prefix RNA: <http://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI_33697> .
@prefix hgnc: <http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=> .
@prefix obo: <http://purl.obolibrary.org/obo/> .
@prefix occursIn: <http://purl.obolibrary.org/obo/BFO_0000066> .
@prefix species: <http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=> .
@prefix orcid: <http://orcid.org/> .

sub:Head {
  this: np:hasAssertion sub:assertion;
    np:hasProvenance sub:provenance;
    np:hasPublicationInfo sub:pubinfo;
    a np:Nanopublication .
}

sub:assertion {
  sub:_1 geneProductOf: entrez:183;
    a Protein: .
  
  sub:_2 geneProductOf: hgnc:2500;
    a RNA: .
  
  sub:_3 rdf:object sub:_2;
    rdf:predicate belv:increases;
    rdf:subject sub:_1;
    a rdf:Statement .
  
  sub:_4 occursIn: obo:CL_0000192, obo:UBERON_0004535, species:9606;
    rdf:object sub:_3;
    rdf:predicate belv:decreases;
    rdf:subject chebi:9150;
    a rdf:Statement .
  
  sub:assertion rdfs:label "a(CHEBI:simvastatin) -| (p(EGID:183) -> r(HGNC:CTGF))",
      "p(EGID:183) -> r(HGNC:CTGF)" .
}

sub:provenance {
  beldoc: dce:description "Approximately 61,000 statements.";
    dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
    dce:title "BEL Framework Large Corpus Document";
    pav:authoredBy sub:_7;
    pav:version "20131211" .
  
  sub:_5 dce:identifier "AHA Abstracts 621";
    dce:title "AHA Abstracts 621";
    dce:type "Other" .
  
  sub:_6 prov:value "3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have shown beneficial effects in the treatment of cardiovascular diseases as lipid lowering drugs. Recent work points to cholesterol-independent actions such as inhibition of isoprenylation and activation of G proteins. Angiotensin II (AngII) participates in the development of fibrosis during vascular damage. Connective tissue growth factor (CTGF) has been described as a novel fibrotic mediator. Our aim was to investigate whether HMG-CoA reductase inhibitors could modulate AngII responses, investigating in vascular smooth muscle cells the effect on CTGF expression. Results: In growth-arrested VSMC, AngII, via AT1 receptor, induced CTGF mRNA expression (Northern) and protein production (5-fold vs control; 10-7 mol/L AngII at 24 h; Western). A CTGF antisense oligonucleotide decreased AngII-induced fibronectin synthesis, suggesting that CTGF could be a mediator of fibrogenic effects of AngII. Pretreatment of VSMC with simvastatin (10-7 mol/L to 10-10mol/L) time and dose-dependently inhibited AngII-induced CTGF production (maximal 10-7mol/L: 80% inhibition vs AngII; Western). The inhibition of CTGF expression was prevented when cells were incubated with mevalonate, geranylgeranylpyrophosphate and, in a lesser extend, with farnesylpyrophospate. Different receptors coupled to G proteins, including AT1, activate p21ras and Rho kinase. Overexpression of dominant negative mutant of RhoA suppressed CTFG induction by AngII. The inhibitor of Rho kinase Y-27632, dose-dependently decreased AngII-induced CTGF production, implicating RhoA as a signaling module downstream of AngII and showing that the Rho-kinase pathway may be a novel target to inhibit AngII signaling. Conclusions: Our data suggest that HMG-CoA reductase inhibitors, via Rho proteins, regulate AngII-induced CTGF, a protein related to the development of fibrosis, suggesting that some of the beneficial effects of these drugs could be due to modulation of AngII-mediated vascular damage, explaining cholesterol independent protective effects.";
    prov:wasQuotedFrom sub:_5 .
  
  sub:_7 rdfs:label "Selventa" .
  
  sub:assertion prov:hadPrimarySource sub:_5;
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}

sub:pubinfo {
  this: dct:created "2014-07-03T14:31:27.386+02:00"^^xsd:dateTime;
    pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}