A new mechanism and strategy for inhibiting thrombus formation in the artery.

he study by Eguchi et al1 in the current issue of the Circulation Journal is intriguing by showing the new findings in the following points: the endothelial cell mitochondrial function is related to the thrombus formation, and the reactive oxygen species (ROS) produced in the endothelial cells enhance the thrombus formation through the endothelial injury and mitochondrial ATP-sensitive potassium (K-ATP) channel opener, which can attenuate thrombus formation by inhibiting endothelial ROS production. In this study, nicorandil was used at a clinically relevant low dose (less than 1 μmol/L). Nicorandil is a hybrid of a nitric oxide (NO) donor and a K-ATP channel opener. Nicorandil acts as both sarcolemmal and mitochondrial K-ATP channel openers.2–4 The authors demonstrate that arterial thrombosis was induced by endothelial injury by FeCl3 in mouse testicular arteries. They demonstrated the inhibitory effect of thrombus formation by adding the KATP channel openers, nicorandil and diazoxide. It is very interesting that the significantly slowed growth of thrombi caused by nicorandil was abolished by the denudation of the endothelial cells, indicating the endothelial contribution to the platelet aggregation. Furthermore, the authors showed that the effect of nicorandil on thrombus formation was attenuated by the mitochondrial K-ATP channel blocker, 5-HD, but not affected by the NO synthase inhibitor, LNAME.