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 ) and is stored in platelet dense granules. P i enters cells from the extracellular fluid through phosphate transporters and may be stored as PolyP. Here we show that high extracellular P i concentration in vitro 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.

[1]  Hao Wei,et al.  2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets , 2020, Cell Death Discovery.

[2]  A. Saiardi,et al.  Inorganic polyphosphate in mammals: where's Wally? , 2020, Biochemical Society transactions.

[3]  T. Renné,et al.  Polyphosphate as a Target for Interference With Inflammation and Thrombosis , 2019, Front. Med..

[4]  W. Stanford,et al.  Simple Silica Column–Based Method to Quantify Inorganic Polyphosphates in Cartilage and Other Tissues , 2018, Cartilage.

[5]  W. Muntean,et al.  Non-enzymatic quantification of polyphosphate levels in platelet lysates and releasates. , 2016, Journal of pharmaceutical and biomedical analysis.

[6]  A. Serrano,et al.  Inorganic polyphosphate in the microbial world. Emerging roles for a multifaceted biopolymer , 2016, World journal of microbiology & biotechnology.

[7]  J. Morrissey,et al.  Polyphosphate, platelets, and coagulation , 2015, International journal of laboratory hematology.

[8]  A. Goodall,et al.  Hyperphosphatemia, Phosphoprotein Phosphatases, and Microparticle Release in Vascular Endothelial Cells. , 2015, Journal of the American Society of Nephrology : JASN.

[9]  R. Manorama,et al.  Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels. , 2013, Blood.

[10]  Stephanie A. Smith,et al.  Inhibition of polyphosphate as a novel strategy for preventing thrombosis and inflammation. , 2012, Blood.

[11]  S. Disthabanchong.  Vascular calcification in chronic kidney disease: Pathogenesis and clinical implication. , 2012, World journal of nephrology.

[12]  W. Wittkowski,et al.  Increased inorganic phosphate induces human endothelial cell apoptosis in vitro. , 2008, American journal of physiology. Renal physiology.

[13]  E. Oldfield,et al.  Human Platelet Dense Granules Contain Polyphosphate and Are Similar to Acidocalcisomes of Bacteria and Unicellular Eukaryotes* , 2004, Journal of Biological Chemistry.

[14]  B. Gazzard,et al.  Pharmacokinetics and Absolute Bioavailability of Oral Foscarnet in Human Immunodeficiency Virus-Seropositive Patients , 1998, Antimicrobial Agents and Chemotherapy.