Contributions
Abstract: PB2518
Type: Publication Only
Background
It is known that glucine-containing peptides (glyprolines) have anticoagulant, antiplatelet and fibrindepolymerizing effects in vitro and in vivo in normal (Ashmarin et al., 2008) and pathological conditions, complicated by thrombosis (metabolic disorders of fat and carbohydrate, including hyperholesterinemia, metabolic syndrome, diabetes mellitus).
Aims
To improve anticoagulation and create antithrombotic effects of glyprolines peptides by inclusion in their structure of leucine molecule from the N- or C-end in conditions of the depression of the function of the anticoagulation system in the development of metabplic syndrome, enhanced by the introduction of thromboplastin into the bloodstream.
Methods
The following methods were used in this study: registration of platelet aggregation, anticoagulant activity by test of activated partial thromboplastin time, total fibrinolytic activity (TFA), enzymatic fibrinolysis (EF), fibrindepolymerization activity (FDPA). The proline- and glycine-containing oligopeptides having a base Pro-Gly-Pro (PGP) with the addition of the amino acid leucine to N- and C- end of peptide molecule were used. All experiments were carried out on rats in accordance with the Helsinki Declaration about humane treatment of animals. The development of metabolic syndrome was modeled by keeping all animals on a high-calorie diet (HCD) for 2 months. Scheme of experiments: the experimental group of rats were intranasally administrated the peptides every 24 h for 5 days at a doses of 500 µg/kg. At the same time the control group of rats were received 0.85% saline instead peptides. 18 h after the last administration of peptides rats intravenously injected 1% thromboplastin in the amount of 0.4 ml to generate thrombin in the bloodstream. Blood samples were taken 6-8 min after injection of thromboplastin.
Results
It was found that PGPL and LPGP inhibit the formation of fibrin clots in the provocation of venous thrombosis. When comparing the antithrombotic action of two peptides, it was found that the process of fibrin polymerization took place more slowly under the action of PGPL than LPGP in these conditions. The blood of animals was analyzed after the action of thromboplastin in the preliminary administration of oligopeptides PGPL and LPGP. The increase in TFA-1.7-1.6 times, EF-1.5-1.4 times, FDPA-1.9-2.7 times compared with control rats contained on the HCD and did not receive peptides were found in the blood. In these experimental conditions, in the case of the fibrin clots formation in the bloodstream, they are rapidly subjected to not only enzymatic (plasmin action), but also non-enzymatic (the action of the peptides themselves) lysis. We have shown that oligopeptides exhibit anticoagulant activity in the bloodstream. The action of PGPL is more pronounced (1.6 times increase), than anticoagulant plasma activity of LPGP (1.36 times increase). Both peptide provided in the blood antiplatelet effect (the most significant after LPGP administration). Thus, platelet aggregation decreased by 55% and 65% under the action of PGPL and LPGP respectively.
Conclusion
Thus, glyproline peptides with leucine included in their structure at both ends of the molecule activate or normalize the function of the blood anticoagulation system. They are involved in the prevention of venous thrombosis processes and contribute to the manifestation of thrombolytic effects of plasmin. They have antiplatelet effect, protecting the organism from the initial stages of thrombosis. Peptide LPGP has the most effective anticoagulant and antithrombotic action.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Fibrinolysis, Peptide, Thrombosis
Abstract: PB2518
Type: Publication Only
Background
It is known that glucine-containing peptides (glyprolines) have anticoagulant, antiplatelet and fibrindepolymerizing effects in vitro and in vivo in normal (Ashmarin et al., 2008) and pathological conditions, complicated by thrombosis (metabolic disorders of fat and carbohydrate, including hyperholesterinemia, metabolic syndrome, diabetes mellitus).
Aims
To improve anticoagulation and create antithrombotic effects of glyprolines peptides by inclusion in their structure of leucine molecule from the N- or C-end in conditions of the depression of the function of the anticoagulation system in the development of metabplic syndrome, enhanced by the introduction of thromboplastin into the bloodstream.
Methods
The following methods were used in this study: registration of platelet aggregation, anticoagulant activity by test of activated partial thromboplastin time, total fibrinolytic activity (TFA), enzymatic fibrinolysis (EF), fibrindepolymerization activity (FDPA). The proline- and glycine-containing oligopeptides having a base Pro-Gly-Pro (PGP) with the addition of the amino acid leucine to N- and C- end of peptide molecule were used. All experiments were carried out on rats in accordance with the Helsinki Declaration about humane treatment of animals. The development of metabolic syndrome was modeled by keeping all animals on a high-calorie diet (HCD) for 2 months. Scheme of experiments: the experimental group of rats were intranasally administrated the peptides every 24 h for 5 days at a doses of 500 µg/kg. At the same time the control group of rats were received 0.85% saline instead peptides. 18 h after the last administration of peptides rats intravenously injected 1% thromboplastin in the amount of 0.4 ml to generate thrombin in the bloodstream. Blood samples were taken 6-8 min after injection of thromboplastin.
Results
It was found that PGPL and LPGP inhibit the formation of fibrin clots in the provocation of venous thrombosis. When comparing the antithrombotic action of two peptides, it was found that the process of fibrin polymerization took place more slowly under the action of PGPL than LPGP in these conditions. The blood of animals was analyzed after the action of thromboplastin in the preliminary administration of oligopeptides PGPL and LPGP. The increase in TFA-1.7-1.6 times, EF-1.5-1.4 times, FDPA-1.9-2.7 times compared with control rats contained on the HCD and did not receive peptides were found in the blood. In these experimental conditions, in the case of the fibrin clots formation in the bloodstream, they are rapidly subjected to not only enzymatic (plasmin action), but also non-enzymatic (the action of the peptides themselves) lysis. We have shown that oligopeptides exhibit anticoagulant activity in the bloodstream. The action of PGPL is more pronounced (1.6 times increase), than anticoagulant plasma activity of LPGP (1.36 times increase). Both peptide provided in the blood antiplatelet effect (the most significant after LPGP administration). Thus, platelet aggregation decreased by 55% and 65% under the action of PGPL and LPGP respectively.
Conclusion
Thus, glyproline peptides with leucine included in their structure at both ends of the molecule activate or normalize the function of the blood anticoagulation system. They are involved in the prevention of venous thrombosis processes and contribute to the manifestation of thrombolytic effects of plasmin. They have antiplatelet effect, protecting the organism from the initial stages of thrombosis. Peptide LPGP has the most effective anticoagulant and antithrombotic action.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Fibrinolysis, Peptide, Thrombosis