Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia

Abstract

An increased number of circulating endothelial cells (CECs) was demonstrated in a-and b-thalassemic patients, b-thalassemia/hemoglobin E (BE), both splenectomized (BE [S]) and non-splenectomized (BE[NS]), had higher numbers of CECs than a-thalassemia, both HbH (a-thal l/a-thal 2; H) and HbH with hemoglobin Constant Spring (a-thal 1/CS; H/CS). CECs were also increased in heterozygous HbE (EA) and homozygous HbE (EE). The highest level of tumor necrosis factor-a (TNF-a) was found in HbH/CS patients, whereas the highest levels of vascular endothelial growth factor (VEGF) was observed in BE [S] patients. Significant decreases, in protein C and protein S levels were found in both aand b-thalassemia compared with normal. Good correlations between the numbers of CEC and TNF-a, VEGF, protein C, and protein S levels were demonstrated in this study. In addition, markers for endothelial cell activation and injury (intercellular adhesion molecule-1, ICAM-1/CD54; vascular cell adhesion molecule-1, VCAM-1/CD106; and E-selectin, ELAM-1/CD62E) were detected on the surface of isolated CECs using immunofluorescence technique. Appearance of CECs with markers for endothelial cell activation, together with increased levels of TNF-a and VEGF and decreased levels of protein C and protein S in the circulation, may account for the propensity of vascular perturbation in thalassemic subjects. Am.

Elevated erythropoietin and cytokines levels are related to impaired reticulocyte maturation in thalassemic patients

“…In this study, we found a negative correlation between L Retic and various erythropoietic inhibitory cytokines such as TNF-α, IFN-γ, IL-10 and VEGF which may reflect the impaired reticulocytes maturation in these thalassemic patients. Recent studied reported that, in vivo IFN-γ neutralization confirmed that IFN-γ contributed to erythropoietic suppression but not reduced red blood cell survival [19] and VEGF which found to be increased in thalassemic patients [47,48] could modulate the hematopoietic system by suppression of BM-hematopoiesis, leading to activation of extramedullary hematopoiesis in the liver and spleen [49]. VEGF levels may be related to the clinical severity of thalassemia intermedia, as expressed by the degree of hepatomegaly and splenectomy [50].…”

The Hemoglobin E Thalassemias

“…4) (Sonakul et al 1980). Thromboembolism in HbE b thalassemia seems to involve platelets, a reactive thalassemic red cell surface, coagulation factors, and abnormal endothelium (Butthep et al 2002;Pattanapanyasat et al 2004). …”

Effects of progressive and maximal exercise on plasma levels of adhesion molecules in athletes with sickle cell trait with or without α-thalassemia

“…Since these hemorheological impairments are thought to increase blood flow resistance in microvessels, they could accelerate endothelial dysfunction and vascular injury (40,41). Soluble adhesion molecules and vascular adhesion phenomena are potential markers of this endothelial activation (5,23). In SCA patients, a combination of the trapping of nondeformable cells and the interactions between sickle reticulocytes, leukocytes, and endothelial cells delay the transit time of RBCs through the capillaries and contribute to the initiation and progression of vasoocclusive crises (3,16,19,23).…”