title: Platelet-derived growth factor is increased in pulmonary capillary hemangiomatosis.
abstract: BACKGROUND
  Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown.
  
  
  METHODS
  We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects. The nodules of proliferating capillaries in PCH patients were needle microdissected from cryostat sections. RNA extraction and labeling were followed by hybridization to U95Av2 oligonucleotide arrays (Affymetrix; Santa Clara, CA). In situ hybridization and immunohistochemistry were also performed.
  
  
  RESULTS
  The gene expression profile of PCH allowed for unsupervised clustering from the profile of the lung tissue samples of control subjects. Platelet-derived growth factor (PDGF)-B gene (PDGFB), PDGF receptor (PDGFR)-beta gene (PDGFR-beta), mast cell-related genes, and type 2 pneumocyte-related genes were found to be overexpressed in PCH lesions. In situ hybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-beta localized to pericytic/vascular smooth muscle cells surrounding the proliferating capillaries. CD117 staining confirmed an abundance of mast cells in the lesions, which also stained heavily for PDGFR-beta.
  
  
  CONCLUSIONS
  The expression of the PDGFB and PDGFR-beta genes characterizes the nodular proliferations of PCH. Increased numbers of mast cells, pericytes, and type II pneumocytes accompany the endothelial proliferation. The up-regulation of these important angiogenic and antiapoptotic genes suggests a mechanism and potential therapeutic approaches for PCH.
authors.affiliation: Departments of Pathology, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Adel M
authors.initials: AM
authors.lastname: Assaad
authors.affiliation: Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.affiliation: Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Selim M
authors.initials: SM
authors.lastname: Arcasoy
authors.affiliation: Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rosenzweig
authors.affiliation: Medicine, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Jessie S
authors.initials: JS
authors.lastname: Wilt
authors.affiliation: Surgery, Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sonett
authors.affiliation: Departments of Pathology, Columbia University College of Physicians and Surgeons, New York, NY.. Electronic address: ab748@columbia.edu.
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
mesh_terms: D000293:Adolescent; D000328:Adult; D002455:Cell Division / Q000235:genetics; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D018324:Hemangioma, Capillary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008866:Microsurgery; D020411:Oligonucleotide Array Sequence Analysis; D020286:Pericytes; D011013:Pneumonectomy; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D020797:Receptor, Platelet-Derived Growth Factor beta