Increased Levels of Circulating Iron-Albumin Complexes in Peripheral Arterial Disease Patients

Abstract

Under physiological conditions, extracellular iron circulates in the blood bound to transferrin. As a consequence of several pathologies, the circulating level of a Non-Transferrin Bound pool of Iron (NTBI) increases. The NTBI pool is biologically heterogeneous and represented by iron chelated either by small metabolites (citrate, amino acids, or cofactors) or by serum proteins. By promoting reactive oxygen species (ROS) and reactive nitrogen species (RNS) formation, NTBI causes oxidative stress and alteration of membrane lipids, seriously compromising the healthy state of organs and tissues. While NTBI involvement in several pathologies has been clarified, its contribution to vascular diseases remains to be investigated. Here we measure and analyze the pool of NTBI in the serum of a small group of peripheral arterial disease (PAD) patients. We show that: (i) the NTBI pool shifts from low molecular complexes to high-molecular ones in PAD patients compared to healthy controls; (ii) most of this NTBI is bound to the serum protein Albumin; (iii) this NTBI-Albumin complex can be isolated and quantitated following a simple immunoisolation procedure amenable to automation and suitable for clinical screening purposes.