Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease

Xiaomei Niu, Mehdi Nouraie, Andrew Campbell, Sohail Rana, Caterina P. Minniti, Craig Sable, Deepika Darbari, Niti Dham, N. Scott Reading, Josef T. Prchal, Gregory J. Kato, Mark T. Gladwin, Oswaldo L. Castro, Victor R. Gordeuk

Research output: Contribution to journalArticle

46 Citations (Scopus)

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. Design and 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≤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.

Original languageEnglish (US)
Article numbere7956
JournalPLoS One
Volume4
Issue number11
DOIs
StatePublished - Nov 23 2009
Externally publishedYes

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sickle cell anemia
Sickle Cell Anemia
vascular endothelial growth factors
platelet-derived growth factor
Pulmonary Hypertension
Tricuspid Valve Insufficiency
Vascular Endothelial Growth Factor A
hypertension
lungs
hemolysis
Left Ventricular Dysfunction
Hemolysis
Hemoglobin oxygen saturation
Plasmas
fibroblast growth factors
Fibroblast Growth Factors
pulmonary artery
interleukin-8
Cell proliferation
interleukin-10

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease. / Niu, Xiaomei; Nouraie, Mehdi; Campbell, Andrew; Rana, Sohail; Minniti, Caterina P.; Sable, Craig; Darbari, Deepika; Dham, Niti; Reading, N. Scott; Prchal, Josef T.; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

In: PLoS One, Vol. 4, No. 11, e7956, 23.11.2009.

Research output: Contribution to journalArticle

Niu, X, Nouraie, M, Campbell, A, Rana, S, Minniti, CP, Sable, C, Darbari, D, Dham, N, Reading, NS, Prchal, JT, Kato, GJ, Gladwin, MT, Castro, OL & Gordeuk, VR 2009, 'Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease', PLoS One, vol. 4, no. 11, e7956. https://doi.org/10.1371/journal.pone.0007956
Niu, Xiaomei ; Nouraie, Mehdi ; Campbell, Andrew ; Rana, Sohail ; Minniti, Caterina P. ; Sable, Craig ; Darbari, Deepika ; Dham, Niti ; Reading, N. Scott ; Prchal, Josef T. ; Kato, Gregory J. ; Gladwin, Mark T. ; Castro, Oswaldo L. ; Gordeuk, Victor R. / Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease. In: PLoS One. 2009 ; Vol. 4, No. 11.
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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. Design and 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≤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.",
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T1 - Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease

AU - Niu, Xiaomei

AU - Nouraie, Mehdi

AU - Campbell, Andrew

AU - Rana, Sohail

AU - Minniti, Caterina P.

AU - Sable, Craig

AU - Darbari, Deepika

AU - Dham, Niti

AU - Reading, N. Scott

AU - Prchal, Josef T.

AU - Kato, Gregory J.

AU - Gladwin, Mark T.

AU - Castro, Oswaldo L.

AU - Gordeuk, Victor R.

PY - 2009/11/23

Y1 - 2009/11/23

N2 - 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. Design and 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≤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.

AB - 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. Design and 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≤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.

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