title: Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis.
abstract: BACKGROUND
  Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by an abnormal proliferation of smooth muscle-like cells (LAM cells) in the lung and along the axial lymphatics. LAM demonstrates a heterogeneous clinical course, but there is no serum surrogate marker available for assessing the disease severity or predicting the disease progression. Since the authors have recently demonstrated the extensive LAM-associated lymphangiogenesis and its potential role in progression and metastasis of LAM cells, they hypothesized that serum levels of lymphangiogenic growth factors might be increased in LAM and become a surrogate marker for disease severity.
  
  
  RESULTS
  VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly increased in LAM patients as compared with age- and gender-matched healthy volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4 approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p<0.0001). Serum VEGF-D levels negatively correlated with variables of pulmonary function tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity) (r=-0.365, p<0.05) and %DLco/VA (the percentage of diffusing capacity for carbon monoxide/alveolar volume to the predicted value) (r=-0.560, p<0.001). As expected, the group who received hormone therapy showed more deteriorated pulmonary function with higher serum VEGF-D levels than the group who was just observed without hormone therapy. Immunohistochemical examination of lung specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D.
  
  
  CONCLUSIONS
  Serum VEGF-D levels may be a valuable surrogate marker for evaluating the disease severity in LAM.
authors.affiliation: Department of Respiratory Medicine, Juntendo University, School of Medicine, and Pneumothorax Center, Nissan Tamagawa Hospital, Tokyo, Japan. kseyama@med.juntendo.ac.jp
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Seyama
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumasaka
authors.forename: Sanae
authors.initials: S
authors.lastname: Souma
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Sato
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kurihara
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitani
authors.forename: Sigeru
authors.initials: S
authors.lastname: Tominaga
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Fukuchi
mesh_terms: D000328:Adult; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006728:Hormones / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism; D018192:Lymphangioleiomyomatosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D012129:Respiratory Function Tests; D014594:Uterine Neoplasms / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D042582:Vascular Endothelial Growth Factor C / Q000097:blood; D042643:Vascular Endothelial Growth Factor D / Q000097:blood* / Q000378:metabolism; D014797:Vital Capacity / Q000187:drug effects / Q000502:physiology
chemical_list: D006728:Hormones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D