From Human Megakaryocytes to Platelets: Effects of Aspirin on High-Mobility Group Box 1/Receptor for Advanced Glycation End Products Axis

Abstract

Platelets (PLTs) are the major source of high-mobility group box 1 (HMGB1), a protein that is involved in sterile inflammation of blood vessels and thrombosis. Megakaryocytes (MKs) synthesize HMGB1 and transfer both protein and mRNA into PLTs and PLT-derived microvesicles (MV). Free HMGB1 found in supernatants of <i>in vitro</i> differentiated MKs and in a megakaryoblastic cell line (DAMI cells). Aspirin "<i>in vivo</i>" and "<i>in vitro</i>" not only reduces HMGB1 and receptor for advanced glycation end products expression on MKs and PLTs but also drives the movement of HMGB1 from MKs into PLTs and PLT-derived MV. These findings suggest that consumption of low doses of aspirin reduces the risk of atherosclerosis complications as well as reducing PLT aggregation by the inhibition of COX-1.