Evidence for a Proatherogenic Biochemical Phenotype in Beta Thalassemia Minor and Intermedia

Abstract

The purpose of this study was to focus on pathophysiological mechanisms linking β-thalassemia intermedia (β-TI) and minor (β-TMI) with cardiovascular risk. Iron status, prooxidant-antioxidant balance and lipid profiles in serum, and lipid content in peripheral blood mononuclear cells (PBMCs) were evaluated in 20 β-TMI subjects, 22 β-TI patients and in 30 nonthalassemic blood donors. The mRNA levels of some genes involved in the regulation of iron and cholesterol metabolism were also determined. In β-TI and in β-TMI, serum iron, prooxidant-antioxidant ratio, transferrin saturation and erythropoietin levels were higher, while transferrin and hepcidin were lower compared to controls. Hepcidin and interleukin-1α mRNA levels were found to be reduced in β-TI- and β-TMI-PBMCs, while those of tumor necrosis factor alpha were increased. A reduction in high-density lipoprotein cholesterol in serum and an accumulation of neutral lipids coupled with increased mRNA levels of acetyl-coenzyme A:cholesterol acyltransferase and decreased neutral cholesterol ester hydrolase in PBMCs were also observed in β-TI and β-TMI compared to controls. Taken together, these findings provide experimental support for the idea that not only β-TI patients but also β-TMI have a proatherogenic biochemical phenotype which may contribute to increase their cardiovascular disease risk.

Foxo3 gene expression and oxidative status in beta-thalassemia minor subjects

“…They found that TAC was significantly lower in BTM subjects than in controls, while TBARS was significantly higher, with significant differences between the β 0 and β + thalassemia traits 11 . In addition, Lai et al reported higher levels of the pro-oxidant/antioxidant ratio in β-thalassemia intermedia and BTM, compared to controls 21 . Differences with the present study may be due to methodological differences and sensitivity of the methods.…”

Deferoxamine stimulates LDLR expression and LDL uptake in HepG2 cells

“…DFO and other iron chelators are commonly used in the treatment of iron overload disorders such as β‐thalassemia . Moreover, β‐thalassemic patients are considered at high atherogenic risk , and interestingly iron chelation therapy may improve arterial function in these patients . Together, these data suggest that iron chelation may constitute a supplement for the prevention or treatment of atherosclerosis.…”

The Role of Immune System in Thalassemia Major: A Narrative Review

“…There has been a proposition that elevated level of IL-1α along with increased level of TNF-α, can be involved in cardiovascular events in TM (69). In addition, abnormal pulmonary function has been associated with higher level of IL-8 and TGF-β in TM patients (70).…”