Changes in hemostatic parameters after intranasal administration of peptide Pro-Gly-Pro

Lyapina, L. A.; Pastorova, V. E.; Оберган, Т.Ю.

doi:10.1007/s10517-007-0358-6

Cited by 4 publications

(5 citation statements)

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“…Moreover, PGP also has the ability to block the angiotensin-converting enzyme (Wang et al 2011), one of the most important proatherogenic factors that catalyzes the reaction of angiotensin II formation and promotes vascular wall remodeling (Montezano et al 2014). A number of Russian studies have also identified the antithrombotic and antiaggregant properties of PGP (Pastorova et al 2001;Lyapina et al 2007;Liapina et al 2010), making its adherence to PHBSP even more promising. The key question remains the nature of embedding RGD and PGP motifs in the base molecule.…”

Section: Resultsmentioning

confidence: 99%

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

Belyaeva¹,

Stepenko²,

Lyubimov³

et al. 2020

RRP

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Relevance: Cardiovascular diseases continue to be the leading cause of premature adult death. Lipid profile and atherogenesis: Dislipidaemia leads to subsequent lipid accumulation and migration of immunocompetent cells into the vessel intima. Macrophages accumulate cholesterol forming foam cells – the morphological substrate of atherosclerosis in its initial stage. Inflammation and atherogenesis: Pro-inflammatory factors provoke oxidative stress, vascular wall damage and foam cells formation. Endothelial and mitochondrial dysfunction in the development of atherosclerosis: Endothelial mitochondria are some of the organelles most sensitive to oxidative stress. Damaged mitochondria produce excess superoxide and H2O2, which are the main factors of intracellular damage, further increasing endothelial dysfunction. Short non-hematopoietic erythropoietin-based peptides as innovative atheroprotectors: Research in recent decades has shown that erythropoietin has a high cytoprotective activity, which is mainly associated with exposure to the mitochondrial link and has been confirmed in various experimental models. There is also a short-chain derivative, the 11-amino acid pyroglutamate helix B surface peptide (PHBSP), which selectively binds to the erythropoietin heterodymic receptor and reproduces its cytoprotective properties. This indicates the promising use of short-chain derivatives of erythropoietin for the treatment and prevention of atherosclerotic vascular injury. In the future, it is planned to study the PHBSP derivatives, the modification of which consists in adding RGD and PGP tripeptides with antiaggregant properties to the original 11-member peptide.

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Section: Resultsmentioning

confidence: 99%

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

Belyaeva¹,

Stepenko²,

Lyubimov³

et al. 2020

RRP

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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

Солдатов

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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Changes in hemostatic parameters after intranasal administration of peptide Pro-Gly-Pro

Cited by 4 publications

References 4 publications

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

Non-hematopoietic erythropoietin-derived peptides for atheroprotection and treatment of cardiovascular diseases

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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