title: Effect of targeted therapy on circulating progenitor cells in precapillary pulmonary hypertension.
abstract: BACKGROUND
  Endothelial dysfunction is key in the development of pulmonary hypertension (PH) and is associated with reduced number of circulating progenitor cells. Studies to date evaluating levels of circulating progenitor cells in PH have provided conflicting results. Current treatment of pulmonary arterial hypertension (PAH) and medical treatment of chronic thromboembolic pulmonary hypertension (CTEPH) targets endothelium dependent signalling pathways. The effect of PAH-targeted therapy on circulating progenitor cells has not been clearly established.
  
  
  OBJECTIVE
  To investigate whether levels of circulating progenitor cells in treatment-naïve patients with PAH or CTEPH differ from healthy subjects and to assess the effect of PAH-targeted therapy on the circulating levels of these progenitors.
  
  
  METHODS
  Thirty controls, 33 PAH and 11 CTEPH treatment-naïve patients were studied. Eighteen patients with PAH and 9 with CTEPH were re-evaluated 6-12months after starting PAH-targeted therapy. Levels of progenitors were measured by flow cytometry as CD45+CD34+and CD45+CD34+CD133+cells.
  
  
  RESULTS
  Compared with controls, the number of circulating progenitor cells was reduced in PAH but not in CTEPH. After 6-12months of treatment, levels of circulating progenitors increased in PAH and remained unchanged in CTEPH. Patients with lower exercise tolerance presented lower levels of circulating progenitors. No other relation was found between levels of progenitors and clinical or hemodynamic parameters.
  
  
  CONCLUSIONS
  Patients with PAH, but not those with CTEPH, present reduced levels of circulating progenitor cells. PAH-targeted therapy increases levels of progenitors in PAH but not in CTEPH, suggesting different involvement of progenitor cells in the pathobiology of these pulmonary hypertensive disorders.
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Jéssica
authors.initials: J
authors.lastname: García-Lucio
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain. Electronic address: tura@clinic.ub.es.
authors.forename: Olga
authors.initials: O
authors.lastname: Tura-Ceide
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Pozo
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pizarro
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ferrer
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Díez
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Coll-Bonfill
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Piccari
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Víctor I
authors.initials: VI
authors.lastname: Peinado
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Joan Albert
authors.initials: JA
authors.lastname: Barberà
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000097:blood* / Q000503:physiopathology / Q000628:therapy; D013234:Stem Cells
keywords: Circulating progenitor cells; PAH-targeted therapy; Treatment-naïve patients