Soluble fms-Like Tyrosine Kinase 1 as a Link Between Angiogenesis and Endothelial Dysfunction in Pediatric Patients With β-Thalassemia Intermedia

• Published in: Clinical and applied thrombosis/hemostasis 2017-11, Vol.23 (8), p.943-950
• Main Authors: Tantawy, Azza Abdel Gawad, Adly, Amira Abdel Moneam, Ismail, Eman Abdel Rahman, Youssef, Omneya Ibrahim, Ali, Mohamed ElSayed
• Format: Article
• Language: English
• Subjects: Adolescent; Angiogenesis; beta-Thalassemia - blood; beta-Thalassemia - pathology; beta-Thalassemia - therapy; Biomarkers - blood; Cardiovascular disease; Child; Cross-Sectional Studies; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Female; Growth factors; Humans; Male; Neovascularization, Physiologic; Placenta Growth Factor - blood; Pulmonary hypertension; Vascular Endothelial Growth Factor Receptor-1 - blood
• ISSN: 1076-0296; 1938-2723
• DOI: 10.1177/1076029617692879

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.