title: Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease.
abstract: BACKGROUND
  Pulmonary hypertension and left ventricular diastolic dysfunction are complications of sickle cell disease. Pulmonary hypertension is associated with hemolysis and hypoxia, but other unidentified factors are likely involved in pathogenesis as well.
  
  
  METHODS
  Plasma concentrations of three angiogenic markers (fibroblast growth factor, platelet derived growth factor-BB [PDGF-BB], vascular endothelial growth factor [VEGF]) and seven inflammatory markers implicated in pulmonary hypertension in other settings were determined by Bio-Plex suspension array in 237 children and adolescents with sickle cell disease at steady state and 43 controls. Tricuspid regurgitation velocity (which reflects systolic pulmonary artery pressure), mitral valve E/Edti ratio (which reflects left ventricular diastolic dysfunction), and a hemolytic component derived from four markers of hemolysis and hemoglobin oxygen saturation were also determined.
  
  
  RESULTS
  Plasma concentrations of interleukin-8, interleukin-10 and VEGF were elevated in the patients with sickle cell disease compared to controls (P<or=0.003). By logistic regression, greater values for PDGF-BB (P = 0.009), interleukin-6 (P = 0.019) and the hemolytic component (P = 0.026) were independently associated with increased odds of elevated tricuspid regurgitation velocity while higher VEGF concentrations were associated with decreased odds (P = 0.005) among the patients with sickle cell disease. These findings, which are consistent with reports that PDGF-BB stimulates and VEGF inhibits vascular smooth muscle cell proliferation, did not apply to E/Etdi.
  
  
  CONCLUSIONS
  Circulating concentrations of angiogenic and pro-Inflammatory markers are altered in sickle cell disease children and adolescents with elevated tricuspid regurgitation velocity, a subgroup that may be at risk for developing worsening pulmonary hypertension. Further studies to understand the molecular changes in these children are indicated.
authors: Center for Sickle Cell Disease, Howard University, Washington, DC, United States of America.
authors: Xiaomei
authors: X
authors: Niu
authors: Mehdi
authors: M
authors: Nouraie
authors: Andrew
authors: A
authors: Campbell
authors: Sohail
authors: S
authors: Rana
authors: Caterina P
authors: CP
authors: Minniti
authors: Craig
authors: C
authors: Sable
authors: Deepika
authors: D
authors: Darbari
authors: Niti
authors: N
authors: Dham
authors: N Scott
authors: NS
authors: Reading
authors: Josef T
authors: JT
authors: Prchal
authors: Gregory J
authors: GJ
authors: Kato
authors: Mark T
authors: MT
authors: Gladwin
authors: Oswaldo L
authors: OL
authors: Castro
authors: Victor R
authors: VR
authors: Gordeuk
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D000860:Hypoxia; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10