FUNCTIONAL ACTIVITY OF PLATELETS IN THE APPLICATION OF OLIGOPEPTIDES CONTAINING РROLINE AND ARGININE
Author(s): ,
Marina Grigorjeva
Affiliations:
Biology,Lomonosov Moscow State University,Moscow,Russian Federation
,
Ludmila Lyapina
Affiliations:
Biology,Lomonosov Moscow State University,Moscow,Russian Federation
,
Tamara Obergan
Affiliations:
Biology,Lomonosov Moscow State University,Moscow,Russian Federation
Tatiana Shubina
Affiliations:
Biology,Lomonosov Moscow State University,Moscow,Russian Federation
EHA Library. Grigorjeva M. Jun 14, 2019; 266592; PF793
Prof. Dr. Marina Grigorjeva
Prof. Dr. Marina Grigorjeva
Contributions
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Abstract

Abstract: PF793

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

The ability of platelets to increase blood aggregation activity is observed in a number of diseases, including diabetes, metabolic syndrome, atherosclerosis, vascular endothelial dysfunction, coronary heart disease, stroke and others. Hyperaggregation of platelet leads to increased blood viscosity, impairment of microcirculation and blood supply to organs, can complicate the disease and lead to increased risk of blood clots, and sudden death due to blockage of a major blood vessel by a blood clot. Optimal functional activity of platelets contributes to the full implementation of the intravascular component of microcirculation, normalization of blood viscosity, restoration of insufficiency of blood supply and reduce the prothrombotic status of the organism. A number of pharmacological agents with antiplatelet activity are known. Our studies have shown that short regulatory proline- and glycine-containing peptides with the addition of various amino acids, including arginine and leucine, have anticoagulant effects in vitro and in vivo.

Aims

To analyze changes in platelet aggregation under the influence of new short proline-containing peptides with the addition of the amino acid arginine from the N-end or in the middle of their molecule and to evaluate the data obtained depending on the peptide structure and the concentrations used in experiments in vitro.

 

Methods

All experiments were conducted on male Wistar rats in accordance with «Internetional Guiding Principals for Biomedical Involving Animals». Samples of peptides Arg-Glu-Arg-Pro-Gly-Pro (RERPGP), Arg-Glu-Arg-Gly-Pro (RERGP), Arg-Pro-Gly-Pro (RPGP), Pyr-Arg-Pro (Pyr-RP) were dissolved in 0.85% saline (as vehicle) at concentrations from 10-1 to 10-4 M and then used to measure platelet aggregation (Born method) in platelet-rich plasma (PRP). PRP was prepared from whole blood of healthy rats, than incubated with peptide solutions for 3 minutes in an aggregometer under stirring. To the control samples of PRP 0.85% saline instead of peptides was added. The measurement of platelet aggregation was started upon the addition of 10-6 M ADP reagent for 5 minutes.

 

Results

The results of our researches indicate that the peptides RERPGP, RERGP, RPGP, Pyr-RP exhibit significant antiplatelet activity expressed to varying degrees in experiments in vitro. The addition of all studied peptides to the rat plasma at a concentration of 10-1 M did not change the ADP aggregation of platelets relative to the control samples. The platelet aggregation was reduced by 6-22% (RERGP), 11-33% (RERPGP), 17-34% (RPGP), 21-55% (Pyr-RP) compared to control when peptides were used at concentrations from 10-2 to 10-4 M.

 

Conclusion

The maximum reduction in ADP-induced platelet aggregation was observed by adding peptides RERPGP, RPGP, Pyr-RP to the plasma, in the structure of which proline was located in close proximity to arginine. The most pronounced effects were noted for Pyr-RP. Thus, the structural features of peptides contribute to the realization of their antiplatelet effects. We believe that proline-containing peptides with the addition of arginine to their molecule can be used as antiplatelet agents in conditions of the organism, characterized by increased functional activity of platelets and tendency to thrombosis. 

Study was supported by RFBR 18-04-00260

 

Session topic: 34. Thrombosis and vascular biology - Biology & Translational Research

Keyword(s): Anti-platelet therapies, Peptide, Platelet aggregation, Thrombosis

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