Abstract
Ulinastatin is widely used in the treatment of pancreatitis and sepsis, because of its excellent anti-inflammatory and antioxidant effects. However, its effects on atherosclerosis, an inflammatory vascular disease, are rarely reported. Therefore, in present study, we explored effects of ulinastatin on monocyte-endothelial adhesion, the initiator of atherosclerosis. We used U937 monocytes and angiotensin II-stimulated human umbilical vein endothelial cells (HUVECs) to build the model of monocyte-endothelial adhesion. Different methods were used to change the function of connexin43 (Cx43), the level of ROS, the activation of JAK2/STAT3 signaling pathway and its downstream MMP2 and MMP9 expression, and then the influences of ulinastatin on U937-HUVECs adhesion and the adhesion molecules were observed. The results showed that ulinastatin could attenuate ROS transmission between the neighboring HUVECs via inhibiting Cx43 function. With the decrease of ROS, JAK2/STAT3 signaling pathway and its downstream MMP2 and MMP9 expression were downregulated. Ultimately, important adhesion molecules expression, such as VCAM-1, ICAM-1, sVCAM-1 and sICAM-1, and U937-HUVECs adhesion, were both reduced. Thus, we can conclude that ulinastatin attenuates adhesion molecules expression and monocyte-endothelial adhesion, mechanism of which is related that ulinastatin inhibits ROS transfer between the neighboring vascular endothelial cells mediated by Cx43, resulting in the inactivation of JAK2/STAT3 signaling pathway, and its downstream MMP2 and MMP9 expression decrease.