Oxidative Stress Is A Key Regulator Of Ectopic Calcifications In Beta-Thalassemic Patients

A surprisingly high percentage of clinical complications affecting beta‐thalassemic (beta‐thal) patients is due to ectopic calcifications. Although this abnormal mineralization is similar to that described in pseudoxanthoma elasticum (PXE), ABCC6 gene mutations have been excluded from the pathogenetic mechanisms. Cultured dermal fibroblasts from beta‐thal patients with and without PXE‐like clinical manifestations have been compared for parameters of redox balance and for the expression of proteins, which have been already associated to soft connective tissue mineralization. Results demonstrate that, in beta‐thal patients, elastic fiber calcification is associated to accumulation of anion superoxide and to increased levels of oxidized proteins and lipids. Possibly, as a consequence of the oxidized environment, carboxylation of the calcification inhibitor, MGP, is impaired. Data suggest that, independently from the primary gene defect, common pathogenetic pathways are associated to ectopic calcifications in PXE and in a number of beta‐thal patients. Research supported by PXE International.