title: Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.
abstract: BACKGROUND
  Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation.
  
  
  METHODS
  Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity.
  
  
  RESULTS
  All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals.
  
  
  CONCLUSIONS
  PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity pattern is not paralleled by pPDGFR-β or PDGF-B patterns. PDGFR-β- and EGFR-immunoreactivity of pulmonary vessels distinguishes PAH patients from controls.
authors.affiliation: Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. mj.overbeek@vumc.nl
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Overbeek
authors.forename: Anco
authors.initials: A
authors.lastname: Boonstra
authors.forename: Alexandre E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: Madelon C
authors.initials: MC
authors.lastname: Vonk
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
authors.forename: Maria P A
authors.initials: MP
authors.lastname: van Berkel
authors.forename: Wolter J
authors.initials: WJ
authors.lastname: Mooi
authors.forename: Ben A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: Laurens S
authors.initials: LS
authors.lastname: Hondema
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.forename: Katrien
authors.initials: K
authors.lastname: Grünberg
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D016022:Case-Control Studies; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000378:metabolism / Q000503:physiopathology; D011667:Pulmonary Veins / Q000378:metabolism / Q000503:physiopathology; D011668:Pulmonary Veno-Occlusive Disease / Q000378:metabolism / Q000503:physiopathology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C512478:EGFR protein, human; D066246:ErbB Receptors; D020797:Receptor, Platelet-Derived Growth Factor beta