Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia.
An increased number of circulating endothelial cells (CECs) was demonstrated in alpha- and beta-thalassemic patients, beta-thalassemia/hemoglobin E (BE), both splenectomized (BE[S]) and non-splenectomized (BE[NS]), had higher numbers of CECs than alpha-thalassemia, both HbH (alpha-thal l/alpha-thal 2; H) and HbH with hemoglobin Constant Spring (alpha-thal 1/CS; H/CS). CECs were also increased in heterozygous HbE (EA) and homozygous HbE (EE). The highest level of tumor necrosis factor-alpha (TNF-alpha) 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 alpha- and beta-thalassemia compared with normal. Good correlations between the numbers of CEC and TNF-alpha, 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-alpha 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.
Hematology Division, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand. rapbt@mahidol.ac.th
Punnee
P
Butthep
Saknarong
S
Rummavas
Raewadee
R
Wisedpanichkij
Sumalee
S
Jindadamrongwech
Suthat
S
Fucharoen
Ahnond
A
Bunyaratvej
D000328:Adult; D015415:Biomarkers; D016228:Endothelial Growth Factors / Q000097:blood*; D004730:Endothelium, Vascular / Q000166:cytology*; D006446:Hemoglobin E / Q000032:analysis; D006447:Hemoglobin H / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D008222:Lymphokines / Q000097:blood*; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D013156:Splenectomy; D013499:Surface Properties; D013789:Thalassemia / Q000097:blood / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D011486:Protein C; D017293:Protein S; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006446:Hemoglobin E; D006447:Hemoglobin H