Serotonin potentiates high-glucose-induced endothelial injury: the role of serotonin and 5-HT2A receptors in promoting thrombosis in diabetes

To clarify the involvement of 5-hydroxytryptamine (5-ht) in promotion of thrombogenesis in diabetes,we examined the inhibitory effect of sarpogrelate,a 5-ht2a receptor antagonist,on thrombus formation in diabetic rats. in streptozotocin-induced diabetic rats,polyethylene tube-induced thrombus formation was enhanced compared with that in normal rats. the thrombogenesis was inhibited by sarpogrelate; cilostazol,a pde3 inhibitor; and aspirin,a cox inhibitor,by 75.8%,42.3%,and 34.3%,respectively. the inhibition by sarpogrelate was more pronounced in diabetic rats than normal ones. high glucose and 5-ht increased the expression of vascular cell adhesion molecule-1 (vcam-1) in human umbilical vein endothelial cells (huvecs) and combination of both high glucose and 5-ht further potentiated the effect. sarpogrelate but not aspirin inhibited the increase in vcam-1 expression induced by high glucose and 5-ht. these findings suggest that 5-ht mediates the enhanced thrombogenesis in diabetes and suggests that a 5-ht2a receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications. © the japanese pharmacological society.