Tantawy Azza Abdel Gawad, Adly Amira Abdel Moneam, Ismail Eman Abdel Rahman, Youssef Omneya Ibrahim, Ali Mohamed ElSayed
1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
2 Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Clin Appl Thromb Hemost. 2017 Nov;23(8):943-950. doi: 10.1177/1076029617692879. Epub 2017 Feb 23.
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.
内皮损伤与中间型β地中海贫血（β-TI）血管并发症的发病机制有关。可溶性fms样酪氨酸激酶1（sFLT-1）是血管内皮生长因子受体（VEGFR）家族的成员。可溶性fms样酪氨酸激酶1是一种抗血管生成蛋白，通过粘附和抑制血管内皮生长因子（VEGF）和胎盘生长因子来诱导内皮功能障碍。本研究的目的是评估35例儿童和青少年β-TI患者的sFLT-1水平，并将其与溶血、铁过载以及心肺并发症的标志物相关联。对患者的研究重点在于心脏病史、脾切除术、输血、螯合/羟基脲治疗、血清铁蛋白和sFLT-1水平。对所有参与者进行了超声心动图检查和颈动脉内膜中层厚度（CIMT）测量。与对照组相比，TI患者的可溶性fms样酪氨酸激酶1显著更高（中位数[四分位间距]，110[80-155]pg/mL对70[60-90]pg/mL；P<.001）。脾切除患者以及有肺动脉高压风险或心脏病的患者的sFLT-1水平高于无此情况的患者（P<.001）。确定了区分有和无肺动脉高压风险或心脏病患者的sFLT-1临界值。接受螯合治疗和/或羟基脲的患者中可溶性fms样酪氨酸激酶1较低。sFLT-1与乳酸脱氢酶、血清铁蛋白、肝脏铁浓度、三尖瓣反流喷射速度和CIMT之间存在显著正相关。我们认为sFLT-1代表了血管生成、内皮功能障碍和亚临床动脉粥样硬化之间的联系。测量sFLT-1作为β-TI血管功能障碍的标志物可能有助于早期识别有更高心肺并发症风险的患者。
