Contributions
Abstract: PB2520
Type: Publication Only
Background
Disorders of lipid metabolism in metabolic syndrome leads to atherothrombosis, accompanied by an increase in blood clotting and a decrease in fibrinolysis. It is known that the amino acids proline, arginine, methionine, leucine and regulatory peptides Pro-Gly-Pro, Pro-Gly, Pro-Gly-Pro-Arg have hypocholesterol effect, thereby reducing the risk of developing the disease, and atherosclerosis. Endogenous tripeptide Pro-Gly-Pro has antithrombotic activity, but it is unstable in the body. Also, the essential amino acid valine is required for the growth and synthesis of body tissues. It is necessary for the normal exchange of nitrogen in the organism and is actively involved in the biosynthesis of cholesterol.
Aims
The aim of this work was to assess anticoagulant-fibrinolytic and antiplatelet effects of the peptide Pro-Gly-Pro-Val (PGPV) on the model of rats with experimental metabolic syndrome (MS).
Methods
White male rats (450-600 g) were used in the study. All experiments were conducted in accordance with ethical principles of the Helsinki Declaration. Inducing metabolic disorders caused a high-calorie diet (HCD), the energy value 130% of the standard diet and 32% fat caloric. The content of rats for 6 weeks on HCD led to the development obesity and increased blood glucose. After 1.5 months, rats were divided into groups (in each group n = 10): Group 1 – HCD rats treated with PGPV in dose 200 µg/kg body weight; Group 2 – untreated HCD rats were given 0.85% saline; Group 3 - healthy rats without treatment on standard feed. PGPV or saline were injected by intranasal way for 20 µl per rat once daily for 10 days. Blood samples were obtained 1 h after the last administration of drugs, after 7 and 14 days after discontinuation of the drug with continuing content on HCD (on 10th, 17th and 24th days of experiments, respectively). ADP-induced platelet aggregation, total fibrinolytic activity (TFA), enzymatic (EFA) and non-enzymatic (NFA) fibrinolytic activity on plates of non-stabilized fibrin and anticoagulant activity (APTT test) were determined in blood plasma.
Results
It was found that the 10-fold intranasal treatment of rats with PGPV peptide led to a significant lengthening of the clot formation time by 2.2 times (by APTT test), an increase in TFA by 89% is due to the growth of EFA by 2.7 times and NFA by 1.6 times compared to the Group 2. Platelet aggregation in Group 1 was lower by 58% compared to HCD rats, but was higher than in healthy animals. 7 days after termination of treatment, the significant increase in anticoagulant and fibrinolytic properties of the plasma remained in the Group 1, compared with the values in the 2nd and 3rd Groups. Thus, the APTT increased 2.6 times, TFA – 2.3 times, EFA 2 times, NFA – 1.6 times. Attention is drawn to the fact of a sharp increase in APTT and TFA, i.e. the ability of the drug to provide anticoagulation effect in the long-term. 24 days after the cancellation of the PGPV anticoagulant and fibrinolytic blood activity in rats of the Group1 remained significantly higher than in the 2nd. Platelets aggregation in Group 1 corresponded to normal values and were lower than in the 2nd Group.
Conclusion
Clear evidence was obtained of the benefits of the introduction of PGPV intranasal rats with metabolic disorders as a therapeutic agent that contributes to the normalization of the hemostatic system and reduces thrombotic complications, namely, reducing the increased ability of platelets to aggregate and increase anticoagulant-fibrinolytic activity.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Blood coagulation, Fibrinolysis, Peptide
Abstract: PB2520
Type: Publication Only
Background
Disorders of lipid metabolism in metabolic syndrome leads to atherothrombosis, accompanied by an increase in blood clotting and a decrease in fibrinolysis. It is known that the amino acids proline, arginine, methionine, leucine and regulatory peptides Pro-Gly-Pro, Pro-Gly, Pro-Gly-Pro-Arg have hypocholesterol effect, thereby reducing the risk of developing the disease, and atherosclerosis. Endogenous tripeptide Pro-Gly-Pro has antithrombotic activity, but it is unstable in the body. Also, the essential amino acid valine is required for the growth and synthesis of body tissues. It is necessary for the normal exchange of nitrogen in the organism and is actively involved in the biosynthesis of cholesterol.
Aims
The aim of this work was to assess anticoagulant-fibrinolytic and antiplatelet effects of the peptide Pro-Gly-Pro-Val (PGPV) on the model of rats with experimental metabolic syndrome (MS).
Methods
White male rats (450-600 g) were used in the study. All experiments were conducted in accordance with ethical principles of the Helsinki Declaration. Inducing metabolic disorders caused a high-calorie diet (HCD), the energy value 130% of the standard diet and 32% fat caloric. The content of rats for 6 weeks on HCD led to the development obesity and increased blood glucose. After 1.5 months, rats were divided into groups (in each group n = 10): Group 1 – HCD rats treated with PGPV in dose 200 µg/kg body weight; Group 2 – untreated HCD rats were given 0.85% saline; Group 3 - healthy rats without treatment on standard feed. PGPV or saline were injected by intranasal way for 20 µl per rat once daily for 10 days. Blood samples were obtained 1 h after the last administration of drugs, after 7 and 14 days after discontinuation of the drug with continuing content on HCD (on 10th, 17th and 24th days of experiments, respectively). ADP-induced platelet aggregation, total fibrinolytic activity (TFA), enzymatic (EFA) and non-enzymatic (NFA) fibrinolytic activity on plates of non-stabilized fibrin and anticoagulant activity (APTT test) were determined in blood plasma.
Results
It was found that the 10-fold intranasal treatment of rats with PGPV peptide led to a significant lengthening of the clot formation time by 2.2 times (by APTT test), an increase in TFA by 89% is due to the growth of EFA by 2.7 times and NFA by 1.6 times compared to the Group 2. Platelet aggregation in Group 1 was lower by 58% compared to HCD rats, but was higher than in healthy animals. 7 days after termination of treatment, the significant increase in anticoagulant and fibrinolytic properties of the plasma remained in the Group 1, compared with the values in the 2nd and 3rd Groups. Thus, the APTT increased 2.6 times, TFA – 2.3 times, EFA 2 times, NFA – 1.6 times. Attention is drawn to the fact of a sharp increase in APTT and TFA, i.e. the ability of the drug to provide anticoagulation effect in the long-term. 24 days after the cancellation of the PGPV anticoagulant and fibrinolytic blood activity in rats of the Group1 remained significantly higher than in the 2nd. Platelets aggregation in Group 1 corresponded to normal values and were lower than in the 2nd Group.
Conclusion
Clear evidence was obtained of the benefits of the introduction of PGPV intranasal rats with metabolic disorders as a therapeutic agent that contributes to the normalization of the hemostatic system and reduces thrombotic complications, namely, reducing the increased ability of platelets to aggregate and increase anticoagulant-fibrinolytic activity.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Blood coagulation, Fibrinolysis, Peptide