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Peptide X, a fragment of the chemokine MCP-1, slows the onset of inflammation and decreases the heart function in rats in the model of ischemia-reperfusion

DOI 10.18127/j20700997-201902-02


M.R. Akhmetshina –
Assistant to Department, Department of Physiology and General Pathology, Faculty of Fundamental Medicine, Lomonosov Moscow State University
M.P. Morozova –
Ph.D. (Biol.), Assistant to Department, Department of Physiology and General Pathology, Faculty of Fundamental Medicine, Lomonosov Moscow State University
E.V. Lukoshkova –
Dr.Sc. (Biol.), Research Scientist, Laboratory of Experimental Pathology of Heart, National Medical Research Center of Cardiology of Ministries of Health of the RF (Moscow)
M.V. Ovchinnikov –
Ph.D. (Chem.), Leading Research Scientist, National Medical Research Center of Cardiology of Ministries of Health of the RF (Moscow)
M.V. Sidorova –
Ph.D. (Chem.), Head of Laboratories of Synthesis of Peptides, National Medical Research Center of Cardiology of Ministries of Health of the RF (Moscow)
T.L. Krasnikova –
Dr.Sc. (Biol.), National Medical Research Center of Cardiology of Ministries of Health of the RF (Moscow)
S.A. Gavrilova –
Ph.D. (Biol.), Associate Professor, Deputy Dean of Faculty, Department of Physiology and General Pathology, Faculty of Fundamental Medicine, Lomonosov Moscow State University

Massive sudden death of cardiomyocytes after the onset of ischemia followed by reperfusion (IR) leads to the development of inflammation, which has a detrimental effect on myocardium reparation. Under conditions described the chemokine branch of inflammation plays an important role, for example, the level of chemokine MCP-1 is dramatically elevated in rats after the IR. MCP-1 in turn recruits proinflammatory monocytes into the area of necrosis, which leads to ambiguous results afterwards.
The aim of present study was to investigate the effect of the structural fragment of MCP-1 (65-76 a.a.) named Peptide X, on heart morpho-functional characteristics. Previously we showed in in vivo and in vitro models that peptide X decreased the monocyte migration into the damaged area.
Myocardial infarction was performed on rats by left coronary artery ligation for 2,5 hours after the operation hearts were reperfused. Peptide X was administrated into the sublingual vein at a dose of 35.7 μg/kg in a volume of 200 μl/kg of rat weight immediately after ligation of the left coronary artery (IR-P-X group). The control infarction group (IR-S) was similarly injected with saline (0,9% NaCl). The functional state of the cardiovascular system was performed on anesthetized rats 72 hours and 28 days after the IR. Hemodynamic parameters were recorded in the program PowerGraph 20 minutes at rest and after the infusion of acetylcholine, dobutamine and phenylephrine in a cumulative mode each for 15 minutes. 24, 72 hours and 28 days after surgery, awaken rats were subjected to ECG recording for 20 minutes before and after the 3-minute cold test to calculate heart rate variability parameters (HRV) in the time domain.
Animals of both groups, undergoing IR, showed a similar to each other significant decrease in almost all hemodynamic parameters at early-time and delayed period after the operation at rest in comparison to intact rats. The effect of Peptide X was observed at a response to dobutamune administration: the extent of heart rate increase was 2-times lower then in IR-S group 72 hours after the IR and 3-times lower was the elevation of relaxation index 28 days after the IR. At a long-term period the tendency to weakening of the sympathetic and parasympathetic control of the heart was observed.
The study we performed, showed that Peptide X, by slowing the onset of inflammation, reduces the contribution of the sympathetic and parasympathetic branches of the autonomic nervous system to the cardiac rhythm, decrease the response of relaxation index to dobutamine administration 28 days after ischemia-reperfusion.

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