Contributions
Abstract: PB2521
Type: Publication Only
Background
Fibrin, which is the basis of the blood clot, is formed from fibrinogen plasma upon the activation by the enzyme thrombin. Stabilization of fibrin in the final stage of coagulation is provided by the factor of the blood coagulation system – transglutaminase, FXIII. Increased fibrinogen concentrations, as well as elevated FXIII activity in the blood, can create dangerous thrombosis situations in the human body. In earlier studies, it was shown that short regulatory peptides, containing proline and glycine (glyprolines) exhibit antithrombotic effects in the organism. In our studies on the model of Wessler thrombosis it was shown that repeated administration of peptides Pro-Gly and Pro-Gly-Pro led to a decrease in the weight of fresh fibrin clots and a decrease in the number of cases of thrombosis. Also, glyprolines have antiplatelet, anticoagulant and fibrinolytic activity in vitro and in vivo, impeding the thrombus formation and slowing blood clotting. However, these effects are short-lived due to the low stability of glyprolines. Adding to the peptide molecule of the amino acid arginine increases its resistance and antithrombotic properties. Herewith the influence of glyprolines on blood coagulation factors such as fibrinogen and fibrinase (FXIIIa) has not been studied enough.
Aims
The aim of this study was to evaluate the effect of the peptides Pro-Gly-Pro (PGP) and Pro-Gly-Arg (PGR) on activity of factor XIII, fibrinogen level and anticoagulant activity of blood and their ability to prevent thrombus formation in healthy organism.
Methods
Experiments were carried out on thirty healthy male rats of Wistar strain (200–220 g body weight) in accordance with ethical principles of the Helsinki Declaration. Three groups of animals were used (in each group n = 10): untreated rats as control (Group 1), PGP-treated rats (Group 2) and PGR-treated rats (Group 3). Peptide-treated rats received PGP or PGR by intranasal way daily during 5 days in doses 1 mg/kg of the body weight in the amount of 20 μL per rat. Untreated rats (control) received 0.85% saline as vehicle in the same volume by intranasal way. Blood samples were obtained 1 h after 5rd administration of drugs. Anticoagulant activity (by APTT test), activity of factor FXIII and levels of fibrinogen were estimated in blood plasma by standard methods using standard assay kits (Technology Standard, Russia).
Results
The multiple 5-fold intranasal administration of PGP led to a decrease in the activity of FXIII by 15% (P < 0.05), and PGR – by 25% (P < 0.01) compared to control. The use of both peptides caused a reduction in fibrinogen levels almost equally by 20% and 25%, respectively, compared to values in the control group (P < 0.05 in both cases). This was accompanied by an increase of anticoagulant activity in the animal blood, since APTT raised by 21% (PGP) and 27% (PGR), respectively (P < 0.01 in both cases). It is noted that the effects of the peptide PGR were more pronounced.
Conclusion
The study demonstrated the inhibitory effect of peptides PGP and PGR on blood coagulation factors due to reduce the level of fibrinogen and decrease of activity of FXIII. Thus, the peptides of the glyproline family, when they appear in the bloodstream, contribute to loosen the strength of fibrin clots in case of their emergence, reduce the prothrombotic potential of the blood and restrict the probability of thrombus formation.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Factor XIII, Fibrinogen, Peptide
Abstract: PB2521
Type: Publication Only
Background
Fibrin, which is the basis of the blood clot, is formed from fibrinogen plasma upon the activation by the enzyme thrombin. Stabilization of fibrin in the final stage of coagulation is provided by the factor of the blood coagulation system – transglutaminase, FXIII. Increased fibrinogen concentrations, as well as elevated FXIII activity in the blood, can create dangerous thrombosis situations in the human body. In earlier studies, it was shown that short regulatory peptides, containing proline and glycine (glyprolines) exhibit antithrombotic effects in the organism. In our studies on the model of Wessler thrombosis it was shown that repeated administration of peptides Pro-Gly and Pro-Gly-Pro led to a decrease in the weight of fresh fibrin clots and a decrease in the number of cases of thrombosis. Also, glyprolines have antiplatelet, anticoagulant and fibrinolytic activity in vitro and in vivo, impeding the thrombus formation and slowing blood clotting. However, these effects are short-lived due to the low stability of glyprolines. Adding to the peptide molecule of the amino acid arginine increases its resistance and antithrombotic properties. Herewith the influence of glyprolines on blood coagulation factors such as fibrinogen and fibrinase (FXIIIa) has not been studied enough.
Aims
The aim of this study was to evaluate the effect of the peptides Pro-Gly-Pro (PGP) and Pro-Gly-Arg (PGR) on activity of factor XIII, fibrinogen level and anticoagulant activity of blood and their ability to prevent thrombus formation in healthy organism.
Methods
Experiments were carried out on thirty healthy male rats of Wistar strain (200–220 g body weight) in accordance with ethical principles of the Helsinki Declaration. Three groups of animals were used (in each group n = 10): untreated rats as control (Group 1), PGP-treated rats (Group 2) and PGR-treated rats (Group 3). Peptide-treated rats received PGP or PGR by intranasal way daily during 5 days in doses 1 mg/kg of the body weight in the amount of 20 μL per rat. Untreated rats (control) received 0.85% saline as vehicle in the same volume by intranasal way. Blood samples were obtained 1 h after 5rd administration of drugs. Anticoagulant activity (by APTT test), activity of factor FXIII and levels of fibrinogen were estimated in blood plasma by standard methods using standard assay kits (Technology Standard, Russia).
Results
The multiple 5-fold intranasal administration of PGP led to a decrease in the activity of FXIII by 15% (P < 0.05), and PGR – by 25% (P < 0.01) compared to control. The use of both peptides caused a reduction in fibrinogen levels almost equally by 20% and 25%, respectively, compared to values in the control group (P < 0.05 in both cases). This was accompanied by an increase of anticoagulant activity in the animal blood, since APTT raised by 21% (PGP) and 27% (PGR), respectively (P < 0.01 in both cases). It is noted that the effects of the peptide PGR were more pronounced.
Conclusion
The study demonstrated the inhibitory effect of peptides PGP and PGR on blood coagulation factors due to reduce the level of fibrinogen and decrease of activity of FXIII. Thus, the peptides of the glyproline family, when they appear in the bloodstream, contribute to loosen the strength of fibrin clots in case of their emergence, reduce the prothrombotic potential of the blood and restrict the probability of thrombus formation.
Session topic: 35. Thrombosis and vascular biology & translational Research
Keyword(s): Antithrombotic Therapy, Factor XIII, Fibrinogen, Peptide