Abstract 12998: Platelet Activation Results in Modulation of microRNA Expression Profile: New Insights into the Pathophysiology of Platelet Activation
BACKGROUND AND AIM: Platelets play a key role in different pathophysiological conditions, including acute coronary syndromes (ACS). Current antithrombotic treatments fail to prevent coronary events in selected patients with ACS, indicating that the mechanisms of platelet activation are not fully elucidated. Platelets are anucleate cell fragments with a number of megakaryocyte-derived mRNAs regulated by various mechanisms, such as mRNA splicing and microRNAs (miRNAs). miRNAs are small, non-coding, RNAs which are sequence-targeted modifiers of gene expression acting via mRNA degradation or translational repression. Recently, the existence of miRNA pathway components in human platelets has been reported. Thus, we have analyzed changes in miRNA expression profiling during platelet activation.
METHODS: Platelet-rich plasma (PRP) from 10 healthy volunteers was filtered using a specific leucocytes removal system; PRP purity was checked and found to be >99%. Platelets were activated with ADP (20μM), Collagen (60µg/mL) or thrombin receptor activating peptide (TRAP, 25μM). Aliquots of platelets were obtained at 0, 60, and 120 minutes following addition of the agonist and processed to determine miRNA expression profile by the Illumina's sequencing-by-synthesis technology RESULTS: Platelet activation resulted in significant miRNA modulation, peaking 2 hours after treatment. Of several hundreds miRNA detected, 84 were significantly regulated (fold-change ≥1.5) by ADP, 84 by Collagen and 183 by TRAP, with 51 miRNAs responding similarly to all three conditions tested.
CONCLUSIONS: These findings indicate, for the first time, a physiological role for miRNAs in regulation of platelet function and provides new insights into the pathophysiology of platelet activation.
- © 2012 by American Heart Association, Inc.