Inorganic polyphosphate: a key modulator of inflammation

S. M. Hassanian*, A. Avan, A. Ardeshirylajimi

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Summary: Inorganic polyphosphate (PolyP) is a molecule with prothrombotic and proinflammatory properties in blood. PolyP activates the NF-κB signaling pathway, increases the expression of cell surface adhesion molecules and disrupts the vascular barrier integrity of endothelial cells. PolyP-induced NF-κB activation and vascular hyperpermeability are regulated by the mammalian target of rapamycin complex-1 (mTORC1) and mTORC2 pathways, respectively. Through interaction with receptor for advanced glycation end products (RAGE) and P2Y1 receptors, PolyP dramatically amplifies the proinflammatory responses of nuclear proteins. Moreover, PolyP-mediated activation of the contact pathway results in activation of the kallikrein–kinin system, which either directly or in cross-talk with the complement system induces inflammation in both cellular and animal systems. Thus, polyP is a novel therapeutic target for the treatment of metabolic and acute/chronic proinflammatory diseases, including severe sepsis, diabetes, cardiovascular disease and cancer. In this review, we discuss recent findings on the inflammatory properties of polyP and propose a model to explain the molecular mechanism of proinflammatory effects of this molecule in different systems.

Original languageEnglish
Pages (from-to)213-218
Number of pages6
JournalJournal of Thrombosis and Haemostasis
Volume15
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017
Externally publishedYes

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