Pharmacological inhibition of LIM kinase pathway impairs platelets functionality and facilitates thrombolysis.

Actin is highly abundant in platelets, and its function is dependent on its structure. Actin filaments (F-actin) are dynamic structures involved in many cellular processes including platelet shape changes and adhesion. The actin cytoskeleton is tightly regulated by actin-binding proteins, which include members of the actin depolymerising factor (ADF)/cofilin family. LIM kinase (LIMK) and its phosphatase slingshot (SSH-1L) regulate actin dynamics by controlling the binding affinity of ADF/cofilin towards actin. We hypothesised that the inhibition of LIMK activity may prevent the changes in platelet shape and their function during activation by controlling the dynamics of F-actin. Our results demonstrate that in platelet, inhibition of LIMK by small LIMK inhibitors controls the level of filamentous actin leading to decreased platelet adhesion and aggregation. These findings encourage further studies on controlling platelet function via the cytoskeleton.