title: Circulating endothelial cells: a new candidate biomarker of irreversible pulmonary hypertension secondary to congenital heart disease.
abstract: BACKGROUND
  Congenital heart disease can be complicated by pulmonary arterial hypertension (PAH), the reversibility of which is often difficult to predict. We recently reported a lung biopsy study showing impaired apoptotic regulation of endothelial cells in irreversible PAH. The objective of the present study was to identify noninvasive biomarkers of endothelial turnover that could be used to identify congenital heart disease patients at risk of irreversible PAH.
  
  
  RESULTS
  Circulating endothelial cells (CECs) isolated with CD146-coated beads and circulating CD34(+)CD133(+) progenitor cells (CPCs) were quantified in peripheral vein, pulmonary artery, and pulmonary vein blood samples from 26 patients with congenital heart disease (16 with reversible PAH [median age 2 years] and 10 with irreversible PAH [median age 9 years]) and 5 control patients. Surgical lung biopsy was performed in 19 cases. As expected, endothelial remodeling was observed in irreversible PAH but not in reversible PAH. CEC and CPC numbers were each similar in the 3 types of blood samples. CEC numbers were significantly higher in patients with irreversible PAH (median 57 CEC/mL) than in patients with reversible PAH and control subjects (median 3 CEC/mL in the 2 groups). In contrast, CPC numbers did not differ among patients with irreversible or reversible PAH and control subjects (median 84, 64, and 44 CPC/10(5) lymphocytes, respectively, in the 3 groups).
  
  
  CONCLUSIONS
  Irreversible PAH in congenital heart disease is associated with endothelial damage and with increased circulating endothelial cell counts. The present study suggests that CECs could be a valuable tool to define therapeutic strategies in congenital heart disease patients with PAH.
authors.affiliation: Paris Descartes University, Faculty of Pharmacy, INSERM U765, Paris, France. david.smadja@egp.aphp.fr
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.forename: Dominique
authors.initials: D
authors.lastname: Israël-Biet
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Séverine
authors.initials: S
authors.lastname: Peyrard
authors.forename: Gabriella
authors.initials: G
authors.lastname: Agnoletti
authors.forename: Pascal R
authors.initials: PR
authors.lastname: Vouhé
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.forename: Marilyne
authors.initials: M
authors.lastname: Lévy
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D007223:Infant; D008297:Male; D011651:Pulmonary Artery / Q000473:pathology
chemical_list: D015415:Biomarkers