Abstract
In order to investigate whether a function of vascular endothelial cells was altered in type 2 diabetes mellitus (DM) rats, mRNA expressions of tissue type plasminogen activator (t-PA), urokinase type PA (u-PA), thrombomodulin (TM), plasminogen activator inhibitor type 1 (PAI-1) in vascular endothelial cell (VECs) were semiquatitated by RT-PCR method using a type 2 DM model Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We used a non-diabetic Long-Evans Tokushima Otsuka (LETO) rat’s cultured VECs for comparison. In OLETF VECs, although t-PA and PAI-1 basal mRNA expressions were not changed, u-PA and TM basal mRNA expressions were significantly decreased in comparison with LETO VECs. When exposured to high glucose (23.6 mM) serum-free culture medium (SFM) for 6 hr, t-PA mRNA expression was slightly increased and u-PA mRNA expression was considerably decreased in LETO VECs. In OLETF VECs, expression of each mRNA was slightly decreased at 6 hr after exposure to high glucose SFM. In addition, u-PA, t-PA or TM mRNA expressions was increased when the OLETF VECs were treated with a type 3 phosphodiesterase (PDE) inhibitor, cilostazol, for 24 hr. In conclusion, the constitutive production of hemostatic factors in VECs might be altered in type 2 DM rats and the sustained high glucose condition may further decrease an ability of fibrinolysis/anticoagulation system of VECs. The type 3 PDE inhibitor may improve abnormality of hemostatic factors in type 2 DM patients. [Jpn J Physiol 55 Suppl:S234 (2005)]
