Thalassemia intermedia is associated with a proatherogenic biochemical phenotype

Objective: Unlike beta thalassemia major (beta-TM) in which cardiac siderosis represents the leading cause of mortality and morbidity, in beta thalassemia intermedia (beta-TI), pulmonary hypertension (PHT) and thrombosis seems to be the major cardiovascular complications. However, the mechanism underlying these complications in beta-TI is still unclear. Endothelial dysfunction, the key early event in atherogenesis, is now emerging as an important cardiovascular risk determiner in beta-TI patients. Among the factors known to affect endothelial function, iron and cholesterol merit particular consideration in patients. Therefore, with the aim to extend our knowledge on the mechanisms connecting atherosclerosis to beta-TI, in this study, we compared lipid and iron metabolism in serum and in peripheral blood mononuclear cells (PBMCs) from beta-TI and beta-TM patients and controls. Methods and results: In this study the iron status and the lipid profile in serum and in peripheral blood mononuclear cells (PBMCs) of 22 adult beta-TI patients were examined, and compared with 70 adult and 50 age-matched controls. Despite the great variability, levels of serum iron and transferrin saturation were significantly higher in beta-TI compared to both controls and beta-TM. By contrast, transferrin and hepcidin levels were lower in beta-TI patients. Changes in serum indicators in beta-TI patients were associated with altered expressions in PBMCs of hepcidin and IL-1 alpha, involved in some way in the regulation of iron homeostasis. In addition beta-TI exhibited a reduction of total and high density lipoprotein cholesterol in serum and of neutral cholesterol ester hydrolase in PBMCs, and an increase of cytoplasmic neutral lipids and mRNA levels of acetyl-coenzymeA:cholesterol acyltransferase. Conclusions: Taken together, these findings provide experimental support for the idea that beta-TI patients exhibit a proatherogenic biochemical phenotype which may contribute to enhance cardiovascular risk in these subjects. (C) 2011 Elsevier Inc. All rights reserved.