title: Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia.
abstract: Endothelial damage has been implicated in the pathogenesis of vascular complications in β-thalassemia intermedia (β-TI). Soluble fms-like tyrosine kinase 1 (sFLT-1) is a member of the vascular endothelial growth factor receptor (VEGFR) family. Soluble fms-like tyrosine kinase 1 is an antiangiogenic protein that induces endothelial dysfunction by adhering to and inhibiting VEGF and placenta growth factor. The aim of this study was to assess the level of sFLT-1 in 35 children and adolescents with β-TI, correlating it with markers of hemolysis and iron overload as well as cardiopulmonary complications. Patients were studied focusing on the history of cardiac disease, splenectomy, transfusion, chelation/hydroxyurea therapy, serum ferritin, and sFLT-1 levels. Echocardiography and measurement of carotid intima-media thickness (CIMT) were done for all participants. Soluble fms-like tyrosine kinase 1 was significantly higher in TI patients compared to the control group (median [interquartile range], 110 [80-155] pg/mL versus 70 [60-90] pg/mL; P < .001). Splenectomized patients and those who had pulmonary hypertension risk or heart disease had higher sFLT-1 levels than those without ( P < .001). The sFLT-1 cutoff value that differentiates patients with and without pulmonary hypertension risk or heart disease was determined. Soluble fms-like tyrosine kinase 1 was lower among patients who received chelation therapy and/or hydroxyurea. Significant positive relations were observed between sFLT-1 and lactate dehydrogenase, serum ferritin, liver iron concentration, tricuspid regurgitant jet velocity, and CIMT. We suggest that sFLT-1 represents a link between angiogenesis, endothelial dysfunction, and subclinical atherosclerosis. Measurement of sFLT-1 as a marker of vascular dysfunction in β-TI may provide utility for early identification of patients at increased risk of cardiopulmonary complications.
authors.affiliation: 1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Azza Abdel Gawad
authors.initials: AAG
authors.lastname: Tantawy
authors.affiliation: 1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Amira Abdel Moneam
authors.initials: AAM
authors.lastname: Adly
authors.affiliation: 2 Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Eman Abdel Rahman
authors.initials: EAR
authors.lastname: Ismail
authors.affiliation: 1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Omneya Ibrahim
authors.initials: OI
authors.lastname: Youssef
authors.affiliation: 1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Mohamed ElSayed
authors.initials: ME
authors.lastname: Ali
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D000072483:Placenta Growth Factor / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D017086:beta-Thalassemia / Q000097:blood* / Q000473:pathology / Q000628:therapy
chemical_list: D015415:Biomarkers; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: cardiopulmonary complications; carotid intima–media thickness; soluble fms-like tyrosine kinase 1; thalassemia intermedia