High extracellular phosphate increases platelet polyphosphate content

Abstract

Platelet-derived extracellular polyphosphate (PolyP) is a major mediator of thrombosis. PolyP is a linear chain of inorganic phosphate (P<i>_i</i>) and is stored in platelet dense granules. P<i>_i</i> enters cells from the extracellular fluid through phosphate transporters and may be stored as PolyP. Here we show that high extracellular P<i>_i</i> concentration <i>in vitro</i> increases platelet PolyP content, in a manner dependent on phosphate transporters, IP6K and V-type ATPases. The increased PolyP also enhanced PolyP-dependent coagulation in platelet-rich plasma. These data suggest a mechanistic link between hyperphosphatemia, PolyP and enhanced coagulation, which may be important in pathologies such as chronic kidney disease.