Denatured Albumin Gains a Function of Regulating Platelet Activity

Abstract

Platelets are blood cells that play a critical role in hemostasis and thrombosis. Serum albumin, which constitutes approximately 50% of plasma proteins, has traditionally been considered non-interactive with platelets and not involved in platelet function. Here, using a molecular force sensor and platelet adhesion and aggregation assays, we show that serum albumin, if denatured, specifically binds to integrin IIb{beta}3 in platelets and transmits platelet contractile forces, regulating platelet activation, adhesion and aggregation as effectively as fibrinogen (the clotting factor I). 0.1% ethanol or 10 {micro}M hydrogen peroxide, physiologically attainable in blood through alcohol intake or disease-elevated oxidative stress, are sufficient to denature albumin into a functional platelet ligand. These findings revealed albumin as a previously unrecognized but important regulator of platelet functions, with broad implications for the thrombotic risk in the context of physiological conditions that induce albumin denaturation.