Effect of heparin on conformation of the β2-microglobulin molecule

Heparin, one of the essential molecules called glycosaminoglycans (GAGs), is the anticoagulant that is commonly used in regular hemodialysis, during which dialysis-related amyloidosis (DRA) may develop. The pathogenic protein, i.e. precursor protein, in DRA is β(2)-microglobulin (β(2)m). Recent studies defined amyloidosis as a protein misfolding disease of precursor proteins including β(2)m. Because the analytic technique capillary electrophoresis can identify molecular variants of the folded β(2)m, i.e. conformational variants, we utilized it to investigate the effect of heparin on β(2)m conformation and thus determined whether heparin can promote DRA development by inducing a conformational change in the amyloidogenic β(2)m molecule. Heparin had a slight but significant effect on intermediate β(2)m conformation but no effect on native β(2)m conformation and on conversion of native to intermediate β(2)m. Our findings thus suggest a possible association of β(2)m with GAGs containing a sulfate moiety, including heparin, in HD patients.