title: Association of soluble fms-like tyrosine kinase-1 with pulmonary hypertension and haemolysis in sickle cell disease.
abstract: The pathophysiology of pulmonary hypertension (PHT) in sickle cell disease (SCD) is probably multifactorial. Soluble fms-like tyrosine kinase-1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. By adhering to and inhibiting VEGF and placenta growth factor, it induces endothelial dysfunction. We sought to evaluate the association of sFLT-1 with clinical complications of SCD. We confirmed that sFLT-1 was significantly elevated in SCD patients compared to healthy, race-matched control subjects. The level of sFLT-1 was significantly higher in patients with PHT, but no association was observed between sFLT-1 and the frequency of acute pain episodes or history of acute chest syndrome. sFLT-1 was correlated with various measures of haemolysis, erythropoietin and soluble vascular cell adhesion molecule-1. By inducing endothelial dysfunction, sFLT-1 may contribute to the pathogenesis of SCD-associated PHT, although this effect does not appear to be independent of haemolysis.
authors.affiliation: Comprehensive Sickle Cell Program Division of Hematology/Oncology Department of Biochemistry and Biophysics Department of Biostatistics Department of Pediatrics, University of North Carolina, Chapel Hill, NC 27599-7305, USA. kataga@med.unc.edu
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.forename: Julia E
authors.initials: JE
authors.lastname: Brittain
authors.forename: Susan K
authors.initials: SK
authors.lastname: Jones
authors.forename: Ryan
authors.initials: R
authors.lastname: May
authors.forename: John
authors.initials: J
authors.lastname: Delaney
authors.forename: Dell
authors.initials: D
authors.lastname: Strayhorn
authors.forename: Payal
authors.initials: P
authors.lastname: Desai
authors.forename: Rupa
authors.initials: R
authors.lastname: Redding-Lallinger
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
authors.forename: Eugene P
authors.initials: EP
authors.lastname: Orringer
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000502:physiology*
chemical_list: D006454:Hemoglobins; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1