title: Circulating fibrocytes are increased in children and young adults with pulmonary hypertension.
abstract: Chronic inflammation is an important component of the fibroproliferative changes that characterise pulmonary hypertensive vasculopathy. Fibrocytes contribute to tissue remodelling in settings of chronic inflammation, including animal models of pulmonary hypertension (PH). We sought to determine whether circulating fibrocytes were increased in children and young adults with PH. 26 individuals with PH and 10 with normal cardiac anatomy were studied. Fresh blood was analysed by flow cytometry for fibrocytes expressing CD45 and procollagen. Fibrocyte numbers were correlated to clinical and haemodynamic parameters, and circulating CC chemokine ligand (CCL)2 and CXC chemokine ligand (CXCL)12 levels. We found an enrichment of circulating fibrocytes among those with PH. No differences in fibrocytes were observed among those with idiopathic versus secondary PH. Higher fibrocytes correlated to increasing mean pulmonary artery pressure and age, but not to length or type of treatment. Immunofluorescence analysis confirmed flow sorting specificity. Differences in plasma levels of CCL2 or CXCL12, which could mobilise fibrocytes from the bone marrow, were not found. We conclude that circulating fibrocytes are significantly increased in individuals with PH compared with controls. We speculate that these cells might play important roles in vascular remodelling in children and young adults with pulmonary hypertension.
authors.affiliation: Dept of Paediatrics, Division of Pulmonary and Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045, USA. michael.yeager@ucdenver.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Yeager
authors.forename: C M
authors.initials: CM
authors.lastname: Nguyen
authors.forename: D D
authors.initials: DD
authors.lastname: Belchenko
authors.forename: K L
authors.initials: KL
authors.lastname: Colvin
authors.forename: S
authors.initials: S
authors.lastname: Takatsuki
authors.forename: D D
authors.initials: DD
authors.lastname: Ivy
authors.forename: K R
authors.initials: KR
authors.lastname: Stenmark
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002469:Cell Separation; D018932:Chemokine CCL2 / Q000097:blood; D054377:Chemokine CXCL12 / Q000097:blood; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood*; D007249:Inflammation; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008648:Mesoderm / Q000166:cytology*; D010586:Phagocytes / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D055815:Young Adult
chemical_list: C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D017493:Leukocyte Common Antigens