Insight into the role of miR-223-3p in regulating platelet reactivity

Objective Platelets have a major role in thrombus formation through their ability to aggregate and to support thrombin generation. During these last years circulating microRNAs (miRNAs), including miR-223-3p, have been suggested as biomarkers to predict clinical outcome in cardiovascular patients. However, the impact of miR-223-3p on the regulation of platelet reactivity is still unclear. This study aims to investigate the relationship between circulating miR-223-3p level, platelet aggregation and in vivo thrombin generation markers, and to identify the putative genes regulated by this miRNA.

Material and Methods MiR-223-3p together with another platelet-derived miRNA (miR-150-5p) was quantified in 191 plasma samples of stable cardiovascular patients. Both miRNAs were normalized against 3 stably expressed endogenous miRNAs previously validated using geNorm algorithm. MiRNAs level was then compared to both in vivo thrombin generation markers and light transmission aggregometry using various agonists including arachidonic acid, ADP and collagen. Finally, a miRNA’s targets network was built based on the gene ontology of pathways implicated in platelet reactivity.

Results MiR-223-3p level was positively associated to both in vivo thrombin generation markers and to ADP and collagen-induced platelet aggregation, while miR-150-5p was associated with platelet aggregation only. The in silico network pointed putative targets that could explain the association between the miRNAs studied and platelet function. This included STMN1, a validated target of miR-223-3p, which could mediate the effect of miR-223-3p on platelet pro-coagulant activity and GLP1R, a predicted target of both miR-223-3p and miR-150-5p known to regulate platelet aggregation.

Conclusion Platelet-derived miRNAs regulate different aspects of platelet reactivity including platelet-supported thrombin generation and platelet aggregation, through regulation of different genes. This study supports the use of a miRNA profile to tailor antithrombotic strategy in cardiovascular patients.

Publication History

Article published online:
18 June 2021