PB1025 - Treatment with Peptide KRRKPGP and Warfarin Changes Anticoagulant Effects and Fibrinolysis in Metabolic Syndrome

Background: Lipid and carbohydrate metabolism disorders, known as metabolic syndrome (MS), are also accompanied by the hemostasis system dysfunction, including hypercoagulation and hypofibrinolysis, which can lead to thrombosis. It has been shown that the treatment with glyproline family peptides (KKRRPGP, RKKRPGP) of MS animals had a positive effect on metabolic processes and hemostatic balance.

Aims: To carry out a comparative analysis of coagulation and fibrinolysis changes undergoing the glyproline peptide Lys-Arg-Arg-Lys-Pro-Gly-Pro (KRRKPGP) and the indirect anticoagulant warfarin treatment of experimental MS.

Methods: Briefly, adult male Wistar rats were fed high-calorie food (3980 kcal/kg, 135% of standard feed) to simulate MS. After 6 weeks, MS-rats were treated with either peptide KRRKPGP or warfarin (intragastric way, 100 μg/kg, once daily, 7 days); MS untreated rats (control) and health rats received 0.85% saline. Than hemostatic parameters of blood plasma were evaluated using standard methods: anticoagulant activity by APTT test and prothrombin time (PT); fibrinolysis was estimated by tests of total fibrinolytic activity (TFA), fibrindepolymerization (FDPA) and enzymatic fibrinolytic activities (EFA).

Results: Feeding animals with high-calorie food for 6 weeks led to increased clotting properties (APTT and PT decreased to 73 and 56%) and inhibition of blood fibrinolysis (TFA, FDPA and EFA amounted to 60, 59 and 50% vs. health rats, respectively). Further peptide KRRKPGP or warfarin treatment resulted in an increase in the anticoagulant activity in both cases (APTT - by 43 and 62% vs. MS-control, respectively), although PT prolongation was observed only after the warfarin application (by 40% vs. MS-control). At the same time, only KRRKPGP-treatment significantly restored of impaired fibrinolysis: the changes of TFA, FDPA and EFA were 193, 176 and 285% vs. MS-control.

Conclusion(s): Thus, warfarin had only anticlotting effects whereas the peptide KRRKPGP contributed to an increase both anticoagulant and fibrinolytic properties of blood when used in the MS conditions.