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ANTIPLATELET AND FIBRINOLYTIC EFFECTS OF ARGININE-CONTAINING PEPTIDES IN HEALTHY RATS AND RATS WITH METABOLIC SYNDROME
Author(s): ,
Yumei Song
Affiliations:
M.V.Lomonosow Moscow State University,Moscow,Russian Federation
,
Marina Grigorjeva
Affiliations:
M.V.Lomonosow Moscow State University,Moscow,Russian Federation
Tamara Obergan
Affiliations:
M.V.Lomonosow Moscow State University,Moscow,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Song Y. 05/18/17; 182930; PB2217
Yumei Song
Yumei Song
Contributions
Abstract

Abstract: PB2217

Type: Publication Only

Background

Currently, the number of diabetes, hypercholesterolemia, metabolic syndrome (MS) patients has increased sharply in the world. MS is metabolic disorders with increase of cholesterol and glucose levels, dyslipemia, endothelial dysfunction. This is accompanied by an increase in blood clotting, including platelet aggregation strengthening and reducing the activity of the plasminogen activator. Thus, the MS may predispose to venous thrombosis. It is known that, regulatory oligopeptides involved in the conservation normal functional activity of coagulation, anticoagulation, insular systems of the organism, fat metabolism. It is also known that some amino acids, particularly arginine, improve rheological properties of blood and reduce platelet aggregation.

Aims
To study the effect of tripeptides Pro-Arg-Gly and Gly-Arg-Pro, containing arginine in the molecule, on platelet aggregation and tissue plasminogen activator (t-PA) activity in a healthy organism and the development of the experimental MS.

Methods
Experiments were carried out on Wistar rats weighing 300-350 g in accordance with the ethical principles of the Helsinki Declaration. Two groups of animals were used: healthy rats and rats with experimental MS. Peptides were intranasal injected in doses of 1 mg / kg once daily for 5 days. 0.85% NaCl solution was injected to control rats in the same time frame. MS in rats was caused by a hyper-cholesterol fat-rich diet (FD) for 6 weeks. Blood samples were taken from the jugular vein 1 hour after the last drug administration. Activity of t-PA (fibrin plate method) and ADP-induced platelet aggregation (standard method) were measured in blood plasma.

Results
The intranasal administration of peptides Gly-Arg-Pro, and Pro-Arg-Gly to healthy animals resulted a reduction of platelet aggregation by 23% and 52% compared with the control. Both peptides induced enhancement t-PA activity of 2 or 3.5 times respectively. In rats with experimental MS these effects were preserved, besides, platelet aggregation was decreased by 27% (Pro-Arg-Gly) and 38% (Gly-Arg-Pro) compared with the control.

Conclusion
We concluded that intranasal administration of tripeptides Pro-Arg-Gly and Gly-Arg-Pro to organism of healthy rats and in rats with experimental MS show antiplatelet and fibrinolytic effects of the blood. Thus, arginine-containing peptides could potentially be used as antithrombotic drugs that protect the organism from the blood coagulation and thrombus formation.

Session topic: 34. Thrombosis and vascular biology

Keyword(s): Thrombosis, Plasminogen, Fibrinolysis, Anticoagulants

Abstract: PB2217

Type: Publication Only

Background

Currently, the number of diabetes, hypercholesterolemia, metabolic syndrome (MS) patients has increased sharply in the world. MS is metabolic disorders with increase of cholesterol and glucose levels, dyslipemia, endothelial dysfunction. This is accompanied by an increase in blood clotting, including platelet aggregation strengthening and reducing the activity of the plasminogen activator. Thus, the MS may predispose to venous thrombosis. It is known that, regulatory oligopeptides involved in the conservation normal functional activity of coagulation, anticoagulation, insular systems of the organism, fat metabolism. It is also known that some amino acids, particularly arginine, improve rheological properties of blood and reduce platelet aggregation.

Aims
To study the effect of tripeptides Pro-Arg-Gly and Gly-Arg-Pro, containing arginine in the molecule, on platelet aggregation and tissue plasminogen activator (t-PA) activity in a healthy organism and the development of the experimental MS.

Methods
Experiments were carried out on Wistar rats weighing 300-350 g in accordance with the ethical principles of the Helsinki Declaration. Two groups of animals were used: healthy rats and rats with experimental MS. Peptides were intranasal injected in doses of 1 mg / kg once daily for 5 days. 0.85% NaCl solution was injected to control rats in the same time frame. MS in rats was caused by a hyper-cholesterol fat-rich diet (FD) for 6 weeks. Blood samples were taken from the jugular vein 1 hour after the last drug administration. Activity of t-PA (fibrin plate method) and ADP-induced platelet aggregation (standard method) were measured in blood plasma.

Results
The intranasal administration of peptides Gly-Arg-Pro, and Pro-Arg-Gly to healthy animals resulted a reduction of platelet aggregation by 23% and 52% compared with the control. Both peptides induced enhancement t-PA activity of 2 or 3.5 times respectively. In rats with experimental MS these effects were preserved, besides, platelet aggregation was decreased by 27% (Pro-Arg-Gly) and 38% (Gly-Arg-Pro) compared with the control.

Conclusion
We concluded that intranasal administration of tripeptides Pro-Arg-Gly and Gly-Arg-Pro to organism of healthy rats and in rats with experimental MS show antiplatelet and fibrinolytic effects of the blood. Thus, arginine-containing peptides could potentially be used as antithrombotic drugs that protect the organism from the blood coagulation and thrombus formation.

Session topic: 34. Thrombosis and vascular biology

Keyword(s): Thrombosis, Plasminogen, Fibrinolysis, Anticoagulants

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