Ther Adv Hematol. 2026 Feb 10;17:20406207261417140. doi: 10.1177/20406207261417140. eCollection 2026.
ABSTRACT
BACKGROUND: Patients with β-thalassemia major remain at risk for endothelial dysfunction and cardiac injury due to iron overload, oxidative stress, and chronic inflammation, even with iron-chelation therapy. Assessing vascular and cardiac serum biomarkers provides a practical tool to understand disease mechanisms and guide management.
OBJECTIVES: This study aims to identify reliable diagnostic markers for endothelial dysfunction in β-thalassemia major patients, a known risk factor for cardiovascular disease.
DESIGN: Case-control, cross-sectional study.
METHODS: Serum markers of endothelial dysfunction and cardiac damage, along with lipid profiles, were assessed. In addition, the expression of genes encoding enzymes related to cellular antioxidant defense and ferroptosis was evaluated.
RESULTS: Sixty transfusion-dependent β-thalassemia major patients on iron-chelation therapy and 20 healthy controls participated in the study. Significant differences among control, splenectomized, and non-splenectomized β-thalassemia groups were observed for erythrocyte sedimentation rate (ESR), high mobility group box 1 (HMGB-1), interleukin-10 (IL-10), interleukin-18, fibroblast growth factor 21 (FGF21), soluble suppression of tumorigenicity 2 (sST2), and soluble vascular cell adhesion molecule-1 (sVCAM-1), but not interleukin-23, interleukin-33, or calprotectin. Receiver operating characteristic (ROC) analysis showed AUCs of 0.991, 0.990, 0.848, and 0.831 for IL-10, ESR, sST2, and sVCAM-1, respectively (p < 0.05). Hypertriglyceridemia with decreased low-density lipoprotein and total cholesterol was noted in β-thalassemia groups. The expression of SLC7A11, KEAP1, and HO-1 genes was elevated, while NRF2 and GPX4 showed no significant change. HO-1 showed a significant inverse correlation with HMGB-1 (r = -0.405, p = 0.001), KEAP1 was positively correlated with sST2 (r = 0.282, p = 0.029), and GPX4 was correlated with FGF21 (r = 0.255, p = 0.049); no other significant associations were found.
CONCLUSION: β-thalassemia major patients exhibit significant endothelial and cardiac injury markers, altered lipid profiles, and selective upregulation of antioxidant and ferroptosis-related genes.
PMID:41685053 | PMC:PMC12891404 | DOI:10.1177/20406207261417140