A single miRNA can regulate many mammalian protein expression levels either by degrading mRNA or repressing translation. Circulating microRNAs (miRNAs) have been proposed as biomarkers for different diseases. One particular miRNA i.e. miR-223, is markedly downregulated in plasma from patients with diabetes or at a high risk of myocardial infarction. miR-223 is one of the most abundant miR in platelets but as little is known about its role therein we set out to study the consequences of miR-223 deletion on platelet function.

Platelets from miR-223^-/- mice demonstrated an enhanced platelet aggregation in response to either thrombin or collagen compared to platelets from wild-type littermates. Moreover, platelets from miR-223^-/- mice developed large aggregates when added to different extracellular matrices and demonstrated a delay in clot retraction. In miR-223^-/- mice, the bleeding time was markedly shorter and a significantly larger thrombus developed after FeCl₃-induced carotid artery injury than in wild-type mice. To identify proteins regulated by miR-223 we compared the proteome of miR-223^-/- and wild-type platelets (2D-DIGE). miR-223^-/- platelets expressed higher levels of kindlin-3, b1 integrin, a2 integrin and factor XIII-A than wild-type platelets. The same changes in protein expression were also detected in platelets from diabetic patients. The α2β1 integrin antagonist; rhodocetin, prevented the changes in platelet aggregation in miR-223-/- platelets and factor XIII-A inhibition normalized the clot retraction process.

In conclusion, our data indicate that miR-223 plays an important role in the regulation of platelet function through targeting integrin signalling and FXIII-A expression and activity.