Microparticles from β-thalassaemia/HbE patients induce endothelial cell dysfunction

Abstract

Thromboembolic complication occurs frequently in β-thalassaemia/HbE patients, particularly in splenectomised patients. Endothelial cells play an important role in thrombosis. There is strong evidence of endothelial cell activation and dysfunction in β-thalassaemia. Microparticles (MPs) are associated with thrombosis and endothelial cell dysfunction in many diseases including β-thalassaemia. However, the effect of thalassaemic-MPs on endothelial cells mediating thrombus formation has not been elucidated. In this study, the effects of circulating MPs from β-thalassaemia/HbE patients on endothelial cell functions were investigated. The results showed that MPs directly induce tissue factor, interleukin (IL)-6, IL-8, intracellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin expression in human umbilical vein endothelial cells (HUVECs). Notably, the levels of these endothelial cell activation markers were significantly increased in HUVECs treated with MPs obtained from splenectomised β-thalassaemia/HbE patients when compared to MPs from non-splenectomised patients or normal subjects. The increased endothelial cell activation ultimately lead to increased monocyte-endothelial cell adhesion. THP-1 and HUVECs adhesion induced by MPs from normal subjects, non-splenectomised and splenectomised patients increased to 2.0 ± 0.4, 2.3 ± 0.4 and 3.8 ± 0.4 fold, respectively when compared to untreated cells. This finding suggests that MPs play an important role on thrombosis and vascular dysfunction in β-thalassaemia/HbE disease, especially in splenectomised cases.

Impact of Activated Monocyte and Endothelial Dysfunction on Coagulopathy in Egyptian Adult Beta Thalassemic Patients

“…Moreover CD11b level, which is a marker of monocytic activation, was significantly lower in patients than controls (P=0.004), these results were in agreement with both. Kheansaard et al, who have studied the origin and the effect of circulating microparticles in thalassemic and reported that the increased microparticles in thalassemia are not monocytic derived and confirmed that other types of MPs play an important role on thrombosis and vascular dysfunction in β-thalassaemia, 18 and Elsayeh et al, who reported an increase in the total MPs in thalassemic patients who had previous history of thrombosis or pulmonary hypertension, however monocytic microparticles did not increase. 19 This finding was explained by Slater et al, who reported that iron overload in thalassemic patients can modulate monocytic functions and activation through inhibition of TLR4 (toll-like receptor 4) which is responsible for monocytes activation by TLR4 -endothelial signaling.…”

Extracellular Vesicles from Red Blood Cells and Their Evolving Roles in Health, Coagulopathy and Therapy

“…BT intermedia and major forms are both associated with a hypercoagulable state and increased incidence of thrombosis [ 157 , 158 ]. Elevated levels of circulating EVs including RBCEVs in BT are reported in multiple studies [ 159 , 160 , 161 , 162 , 163 , 164 , 165 ]. In splenectomized BT patients, a significant increase in the number of circulating RBCEVs is observed compared to non-splenectomized patients [ 159 , 160 , 164 , 165 ].…”

Extracellular Vesicle MicroRNA That Are Involved in β-Thalassemia Complications

“…Higher apoptotic rate and caspase 3/7 activity and reduced viability were observed in endothelial, liver, and pancreatic cells after stimulation with βT vs. control EVs. Previously, Kheansaard and his colleagues demonstrated that microparticles from individuals with βT/HbE induce EC dysfunction [ 32 ]. Our group previously demonstrated that monocyte-derived EVs induce apoptosis in ECs [ 33 ].…”