title: Characterization of proximal pulmonary arterial cells from chronic thromboembolic pulmonary hypertension patients.
abstract: BACKGROUND
  Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with proximal pulmonary artery obstruction and vascular remodeling. We hypothesized that pulmonary arterial smooth muscle (PASMC) and endothelial cells (PAEC) may actively contribute to remodeling of the proximal pulmonary vascular wall in CTEPH. Our present objective was to characterize PASMC and PAEC from large arteries of CTEPH patients and investigate their potential involvement in vascular remodeling.
  
  
  METHODS
  Primary cultures of proximal PAEC and PASMC from patients with CTEPH, with non-thromboembolic pulmonary hypertension (PH) and lung donors have been established. PAEC and PASMC have been characterized by immunofluorescence using specific markers. Expression of smooth muscle specific markers within the pulmonary vascular wall has been studied by immunofluorescence and Western blotting. Mitogenic activity and migratory capacity of PASMC and PAEC have been investigated in vitro.
  
  
  RESULTS
  PAEC express CD31 on their surface, von Willebrand factor in Weibel-Palade bodies and take up acetylated LDL. PASMC express various differentiation markers including α-smooth muscle actin (α-SMA), desmin and smooth muscle myosin heavy chain (SMMHC). In vascular tissue from CTEPH and non-thromboembolic PH patients, expression of α-SMA and desmin is down-regulated compared to lung donors; desmin expression is also down-regulated in vascular tissue from CTEPH compared to non-thromboembolic PH patients. A low proportion of α-SMA positive cells express desmin and SMMHC in the neointima of proximal pulmonary arteries from CTEPH patients. Serum-induced mitogenic activity of PAEC and PASMC, as well as migratory capacity of PASMC, were increased in CTEPH only.
  
  
  CONCLUSIONS
  Modified proliferative and/or migratory responses of PASMC and PAEC in vitro, associated to a proliferative phenotype of PASMC suggest that PASMC and PAEC could contribute to proximal vascular remodeling in CTEPH.
authors.affiliation: Center for Pulmonary Vascular Diseases, Respiratory Disease Department, Katholieke Universiteit and Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
authors.forename: Rozenn
authors.initials: R
authors.lastname: Quarck
authors.forename: Marijke
authors.initials: M
authors.lastname: Wynants
authors.forename: Alicja
authors.initials: A
authors.lastname: Ronisz
authors.forename: Maria Rosario
authors.initials: MR
authors.lastname: Sepulveda
authors.forename: Frank
authors.initials: F
authors.lastname: Wuytack
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Raemdonck
authors.forename: Bart
authors.initials: B
authors.lastname: Meyns
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002908:Chronic Disease; D003893:Desmin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000473:pathology*; D011655:Pulmonary Embolism / Q000473:pathology*; D024745:Smooth Muscle Myosins / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D003893:Desmin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D024745:Smooth Muscle Myosins