The Value of SIRT1/FOXO1 Signaling Pathway in Early Detection of Cardiovascular Risk in Children with β-Thalassemia Major

Abstract

Background: Atherosclerosis represents one of the major causes of morbidity in children with β-thalassemia major (β-TM). Aim: This study was designed to investigate SIRT1-FOXO1 signaling in β-TM children and their role in early detection of premature atherosclerosis. Methods: We equally subdivided 100 Egyptian children aged 6–14 years with β-TM according to carotid intima media thickness (CIMT) into 50 with CIMT < 0.5 mm and 50 with CIMT ≥ 0.5 mm, and 50 healthy children of matched age were included. They were subjected to evaluation of SIRT1, heat shock protein 72 (HSP72), and hepcidin levels via ELISA and forkhead box protein 1 (FOXO1) mRNA expression using real-time PCR in PBMCs; meanwhile, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase activities were evaluated spectrophotometrically. Results: Our results show significantly high values for CIMT, β-stiffness, atherogenic index of plasma (AIP), MDA, HSP72 and FOXO1, ferritin with significantly low hepcidin, SOD, catalase, and SIRT1 in β-TM as compared to controls with a more significant difference in β-TM with CIMT ≥ 0.5 mm than those with CIMT < 0.5 mm. A significant positive correlation between CIMT and MDA, HSP72, and FOXO1 gene expression was found, while a significant negative correlation with hepcidin, SOD, catalase, and SIRT1 was found. FOXO1 gene expression and HSP72 levels were the strongest independent determinants of CIMT. Conclusion: In β-TM, FOXO1 signaling is activated with low levels of SIRT1, and this is attributed to accelerated atherosclerosis in β-TM, which would be crucial in prediction of atherosclerosis.