title: Abnormal pulmonary endothelial cells may underlie the enigmatic pathogenesis of chronic thromboembolic pulmonary hypertension.
abstract: BACKGROUND
  Chronic thromboembolic pulmonary hypertension results from chronic mechanical obstruction of the pulmonary arteries after acute venous thromboembolism. However, the mechanisms that result in the progression from unresolved thrombus to fibrotic vascular remodeling are unknown. We hypothesized that pulmonary artery endothelial cells contribute to this phenomenon via paracrine growth factor and cytokine signaling.
  
  
  METHODS
  Using enzyme-linked immunosorbent assay and cell migration assays, we investigated the circulating growth factors and cytokines of chronic thromboembolic pulmonary hypertension patients as well as the cross talk between pulmonary endothelial cells and pulmonary artery smooth muscle cells and monocytes from patients with chronic thromboembolic pulmonary hypertension in vitro.
  
  
  RESULTS
  Culture medium from the pulmonary endothelial cells of chronic thromboembolic pulmonary hypertension patients contained higher levels of growth factors (fibroblast growth factor 2), inflammatory cytokines (interleukin 1β, interleukin 6, monocyte chemoattractant protein 1), and cell adhesion molecules (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1). Furthermore, exposure to the culture medium of pulmonary endothelial cells from patients with chronic thromboembolic pulmonary hypertension elicited marked pulmonary artery smooth muscle cell growth and monocyte migration.
  
  
  CONCLUSIONS
  These findings implicate pulmonary endothelial cells as key regulators of pulmonary artery smooth muscle cell and monocyte behavior in chronic thromboembolic pulmonary hypertension and suggest a potential mechanism for the progression from unresolved thrombus to fibrotic vascular remodeling.
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; Departments of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Le Plessis Robinson, France. Electronic address: o.mercier@ccml.fr.
authors: Olaf
authors: O
authors: Mercier
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Jennifer
authors: J
authors: Arthur Ataam
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; Departments of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Nathaniel B
authors: NB
authors: Langer
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; Pathology, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Peter
authors: P
authors: Dorfmüller
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Lilia
authors: L
authors: Lamrani
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Florence
authors: F
authors: Lecerf
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Benoit
authors: B
authors: Decante
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; Departments of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Philippe
authors: P
authors: Dartevelle
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; INSERM U1046, CNRS UMR 9214, Université de Montpellier, CHU Arnaud de Villeneuve Montpellier, Montpellier, France.
authors: Saadia
authors: S
authors: Eddahibi
authors: Research and Innovation Unit, INSERM U999, DHU TORINO, Paris Sud University, Marie Lannelongue Hospital, Le Plessis Robinson, France; Departments of Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, Le Plessis Robinson, France.
authors: Elie
authors: E
authors: Fadel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000502:physiology; D012016:Reference Values; D013923:Thromboembolism / Q000150:complications / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins
keywords: adhesion molecules; chronic thromboembolic pulmonary hypertension; cytokine signaling; growth factors; pathogenesis; pulmonary artery endothelial cells; venous thromboembolism