Protective antithrombotic effects of proline-containing peptides under the influence of stress on the animal organism

Lyapina, L. A.; Григорьева, М.Е.; Andreeva, L. A.; Myasoedov, N. F.

doi:10.1134/s1062359010040096

Cited by 9 publications

(4 citation statements)

References 7 publications

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“…С учетом экспрессии MC1R на поверхности тучных клеток [21] правомочно предполагать, что АКТГ 6-9 -ПГП также может снижать проницаемость кишечника за счет местного действия через снижение активности тучных клеток. Также фрагмент АКТГ 6-9 и глипролин Pro-Gly-Pro обладают антикоагулянтной, фибринолитической, антитромбоцитарной активностью [22,23], что может способствовать улучшению микроциркуляции и предотвращению развития дистрофических изменений в стенке толстой кишки.…”

Section: Discussionunclassified

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

et al. 2023

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Aim. To study the morphofunctional state of the colonic wall in rats when using the N–terminal analog of the adrenocorticotropic hormone (ACTH) ACTH6-9-Pro-Gly-Pro (ACTH6-9-PGP) peptide under chronic stress.Materials and methods. The study was performed on 55 male Wistar rats, which were divided into 5 groups (n = 11): group 1 – control group (administration of saline solution without stress); group 2 – chronic restraint stress (CRS) + administration of saline solution; group 3 – CRS + administration of ACTH6-9-PGP at a dose of 5 μg / kg; group 4 – administration of ACTH6-9-PGP at a dose of 50 μg / kg; group 5 – administration of ACTH6-9- PGP at a dose of 500 μg / kg. A histologic examination of the rat colon was performed. The histologic architecture of the colonic wall, the depth of crypts, and the number of goblet cells were assessed. Furthermore, the number of granulocytes, plasma cells, lymphocytes, macrophages, and mast cells was counted.Results. The study demonstrated that chronic (14 days) restraint stress resulted in the development of inflammations in the colonic wall of the animals. Intraperitoneal administration of ACTH6-9-PGP at doses of 50 and 500 μg / kg daily throughout the entire time of stress exposure prevented the development of stress-induced alterations observed in the control animals. At the same time, anti-inflammatory effects of the peptide in the colonic wall and a decrease in the level of corticosterone in the blood serum were noted.Conclusion. The results of this work and data from other studies on the effects of N-terminal analogs of ACTH indicate the need for studying the mechanisms of their effect on inflammation and searching for targets of ACTH6-9-PGP.

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Section: Discussionunclassified

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

et al. 2023

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“…В ряде отечественных работ также были выявлены антитромботические и антиагрегантные свойства другого вспомогательного аминокислотного трипептида Pro-Gly-Pro. [23][24][25]. Кроме того, Pro-Gly-Pro стабилизирует молекулу в биологических средах за счет ингибирования активности протеолитических ферментов [26] и обладает способностью блокировать ангиотензин-превращающий фермент [27], один из важнейших проатерогенных факторов, который катализирует реакцию образования ангиотензина II и способствует ремоделированию сосудистой стенки [28].…”

Section: Discussionunclassified

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Korokin

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Титце

et al. 2020

Farm. farmakol. (Pâtigorsk)

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The aim of the study was to test whether P-αB can be positioned as a preventing and treating agent for cardiovascular diseases.Materials and methods. The study was performed on sexually mature male Wistar rats. Endothelial dysfunction was modulated by a 7-days intraperitoneal administration of L-NAME at the dose of 2.5 mg/100 g. P-αB, or erythropoietin (EPO), was used for therapy at the dose of 2.5 µg/100 g × 3 times for 7 days, the total dose was 7.5 µg/100 g. The function of endothelium was estimated by an endothelium-dependent and endothelium-independent vasodilation. In addition, a histological assessment of the abdominal aortic wall state and the analysis of eNos, Tnf and Il-1β genes expression were performed. To estimate prothrombotic properties, P-αB and EPO were administered, at the doses of 2.5 and 5 µg/100 g (3 times a day for 7 days, the total doses were 7.5 µg/100 g and 15 µg/100 g, respectively) and on the 8th day, the time of ferric (III) chloride-induced carotid artery thrombosis was estimated.Results. Theresults of the functional tests for endothelium-dependent and endothelium-independent vasodilatation, as well as the histological picture of the aorta have evidenced that P-αB and EPO do not affect L-NAME-induced hypertension but improve the endothelium function. At the same time, P-αB shows a significantly higher endothelial-protective activity, reducing the coefficient of endothelial dysfunction from 5.1±0.15 to 2.72±0.12. In addition, P-αB has significantly increased the expression of eNos and reduced the expression level of Tnf and Il-1β mRNA genes. Carrying out Ferric (III) chloride-induced carotid artery thrombosis has revealed that P-αB (5 µg/100 g × 3 times a day for 7 days, total dose was 15 µg/100 g) has a lower but statistically significant prothrombotic activity than EPO.Conclusion. P-αB can be positioned as an atheroprotector because of its ability to prevent the death of endothelial cells, as well as to reduce remodeling and proinflammatory activation of the vascular wall. However, the prothrombotic properties of P-αB limit its use as a preventing and treating agent for atherosclerosis-associated diseases.

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“…Moreover, PGP can also block the angiotensin-converting enzyme [ 50 ], one of the most important pro-atherogenic factors that catalyze the formation of angiotensin II, increasing the risk of brain stroke [ 51 ]. Several studies have also identified antithrombotic and antiplatelet properties of PGP [ 52 , 53 , 54 ], which makes it even more promising to join pHBSP. The key question remains the nature of embedding RGD and PGP motifs in the base molecule.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

Korokin

Гуреев

Гудырев

et al. 2020

IJMS

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Preeclampsia is a severe disease of late pregnancy. Etiological factors and a pathogenetic pattern of events still require significant clarification, but it is now recognized that a large role is played by placentation disorders and emerging endothelial dysfunction. The administration of short-chain peptides mimicking the spatial structure of the B erythropoietin chain may become one of the directions of searching for new drugs for preeclampsia prevention and therapy. Simulation of ADMA-like preeclampsia in Wistar rats was performed by the administration of a non-selective NOS blocker L-NAME from the 14th to 20th day of pregnancy. The administration of the pHBSP at the doses of 10 µg/kg and 250 µg/kg corrected the established morphofunctional disorders. The greatest effect was observed at a dose of 250 µg/kg. There was a decrease in systolic and diastolic blood pressure by 31.2 and 32.8%, respectively (p < 0.0001), a decrease in the coefficient of endothelial dysfunction by 48.6% (p = 0.0006), placental microcirculation increased by 82.8% (p < 0.0001), the NOx concentration was increased by 42,6% (p = 0.0003), the greater omentum edema decreased by 11.7% (p = 0.0005) and proteinuria decreased by 76.1% (p < 0.0002). In addition, there was an improvement in the morphological pattern of the fetoplacental complex and the ratio of BAX to Bcl-2 expression which characterizes the apoptotic orientation of the cells.

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Protective antithrombotic effects of proline-containing peptides under the influence of stress on the animal organism

Cited by 9 publications

References 7 publications

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

Effects of the ACTH<sup>6-9</sup>-Pro-Gly-Pro peptide on the morphofunctional state of rat colon under conditions of chronic restraint stress

11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats.

Erythropoietin Mimetic Peptide (pHBSP) Corrects Endothelial Dysfunction in a Rat Model of Preeclampsia

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