A role for platelet shape change in the efficiency of aspirin/dipyridamole treatment of stroke patients?
Stroke patients have particular high risk of thrombotic events caused by platelet (thrombocyte) activation, which may lead to new infarctions. Secondary treatment of these patients with anti-platelet therapy consisting of aspirin and dipyridamole is therefore a common protocol.
Recent results on the mechanism of action of this treatment suggest that regulation of platelet shape change, the initial step in platelet activation, can play a role in efficiency of this protocol.
Platelets play an important part of our haemostatic machinery, which is necessary to stop bleeding upon damage of our blood vessels. However, excessive activation of platelets may lead to formation of thrombi that may clog the arteries and cause infarction. Inhibition of platelet activation is mainly mediated through cyclic nucleotide signaling (cGMP and cAMP) which are downstream effectors of nitric oxide (NO) and prostaglandins. The endothelial cells of the vascular wall secrete these inhibitory factors (mainly NO and prostacyclin), thereby keeping platelets in check through intracellular sGMP and cAMP signaling. We have previously reported that NO inhibits the initial step of platelet activation (platelet shape-change) through cGMP->cAMP->PKA->VASP signaling. In a recently published paper we report that this cyclic nucleotide cross-talk is strongly amplified by dipyridamole in purified human platelets and PKA activation is necessary for this beneficial effect.