Elevation of Intracellular cAMP Up-Regulated Thrombomodulin mRNA in Cultured Vascular Endothelial Cells Derived from Spontaneous Type-II Diabetes Mellitus Model Rat

To investigate whether antihemostatic function of vascular endothelial cells (VECs) is changed in type-II diabetic model rats, the mRNA expressions of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA), thrombomodulin (TM), PA inhibitor type-1 (PAI-1), and phosphodiesterases (type 3A, 3B, and 4D PDEs) were quantitated by the method of comparative reverse transcriptase–polymerase chain reaction (RT-PCR). VECs from type-II diabetic model Otsuka Long-Evans Tokushima Fatty (OLETF) rats and from its normal counterpart (LETO) rats were cultured for 24 h with dibutyryl adenosine 3′,5′-cyclic monophosphate (db-cAMP) or a type-3 PDE inhibitor, cilostazol. Intracellular cAMP concentration was determined by the chemiluminescent enzyme-linked immunosorbent assay (ELISA) system. In cultured VECs from OLETF rats, the basal mRNA expressions of u-PA and TM were significantly decreased as compared to those in cultured VECs from LETO rats. TM mRNA expression in cultured VECs from OLETF rats was increased ...