Association of Endothelial Dysfunction and Angiogenesis in Patients with Thalassemia Intermedia

Abstract

Abstract 1084 Background:Angiogenic growth factors, such as the vascular endothelial growth factor (VEGF) family of proteins, govern numerous aspects of vessel homeostasis. Placental growth factor (PlGF) is a member of the VEGF family of angiogenic proteins and is expressed in placental, cardiac, and lung tissue. Placental growth factor (PlGF) and its receptor the fms-like tyrosine kinase receptor 1 (Flt-1 or VEGF-R1) are novel therapeutic targets for angiogenic disorders. These growth factors exert pleiotropic effects, potentially beneficial, such as the promotion of angiogenesis, and/or potentially harmful pro-inflammatory effects, such as the promotion of endothelial dysfunction and pulmonary hypertension. von Willebrand factor (vWF) has been proposed as a biomarker of endothelial damage/dysfunction because increased plasma levels have been found in inflammatory and atherosclerotic vascular diseases and is defined as a novel link between hemostasis and angiogenesis.Patients and Methods: We investigated if alterations in angiogenic growth factors may contribute to endothelial dysfunction in patients with thalassemia intermedia (TI) using peripheral biomarkers. Thirty-four adult patients with TI were included in the study, while 20 healthy individuals served as controls. Markers of inflammation such as high-sensitivity C-reactive protein (hs-CRP) and serum Amyloid A protein (SAA), along with markers of endothelial dysfunction such as von Willebrand factor and nitric oxide (NO) and angiogenesis such as PlGF and soluble Flt-1 (sFlt-1) were measured in patients and controls by means of nephelometric, colorimetric and electrochemiluminescence immunoassays, while tissue hypoxia was evaluated in terms of hemoglobin oxygen affinity (P50). Results:The main results of the study showed that: a) plasma levels of vWF, NO, PlGF and sFlt-1 were significantly higher in patients with TI compared to controls (88.0±21.8 vs 71.1±21.5 IU/dL, 101.5±34.7 vs 52.1±8.2 mmol/L, 52.2±20.0 vs 17.2±4.0 pg/mL and 96.5±25.2 vs 76.8±11.5 pg/mL, respectively (p<0.01), while angiogenic balance expressed as sFlt-1/PlGF was significantly lower in patients with TI compared to controls (p<0.0001), b) in patients with TI the plasma levels of vWF correlated significantly with: NO (r=0.535, p<0.001), PlGF (r=0.478, p=0.004) and sFlt-1 (r=0.609, p<0.0001), while no associations were found between vWF with Hb and Hb F levels and c) both PlGF and sFlt-1 levels correlated significantly with NO levels (r=0.571, p<0.001 and r=0.482, p=0.004, respectively) and d) sFlt-1/PlGF correlated significantly with Hb F levels (r=0.385, p=0.02) and with P50 values (r=0.365, p<0.05). Conclusions:These results demonstrate for first time the important link between endothelial dysfunction and angiogenesis in patients with TI. τhe decreased sFlt-1/PlGF ratio in almost all patients with TI suggests that the pro- and anti-angiogenic system is shifted towards the pro-angiogenic state, providing evidence that the factors contributing in this dysregulation are low-grade inflammation and tissue hypoxia. Disclosures:No relevant conflicts of interest to declare.