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Ve, Pastorova; La, Liapina; Ip, Alshmarin; Pu, Ostrovskaia; Gudasheva, T. A.; Ev, Lugovskoĭ

doi:10.1023/a:1016700412205

Cited by 4 publications

(3 citation statements)

References 10 publications

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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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“…Taking into account the fact that the malfunction of the hemostasis system, in particular, the disruption of the aggregation ability of platelets plays a special part in the pathogenesis of preeclampsia and its complications, interesting polypeptide motifs are represented by RGD (Arg-Gly-Asp), KGD (Lys-Gly-Asp), and PGP (Pro-Gly-Pro). which are known for their anti-aggregation properties (Pastorova et al 2001;Lyapina et al 2007;Liapina et al 2010;Kuo et al 2019). The resulting derivatives were the object of the study described in the present paper.…”

mentioning

confidence: 84%

“…Such a pharmacological agent is 11-amino acid peptide pHB-SP (PubChem CID: 91810664), which is an amino acid chain QEQLERALNSS (Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser), having a selective affinity for the heterodimer complex EPOR/CD131 (Hache et al 2016). The short peptide chain allows its modification by adding the polypeptide motifs RGD (Arg-Gly-Asp), KGD (Lys-Gly-Asp) and PGP (Pro-Gly-Pro), which are known for their anti-aggregation properties (Pastorova et al 2001;Lyapina et al 2007;Liapina et al 2010;Obergan et al 2019;Kuo et al 2019). The key issue remains the retention of protective properties of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin after embedding RGD, KGD and PGP motifs into the base molecule.…”

Section: Introductionmentioning

confidence: 99%

Preclinical study of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin

Golubev¹,

Гуреев²,

Корокин³

et al. 2020

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Introduction: The aim of this study was to examine the effectiveness of innovative peptides obtained by addition of polypeptide motifs with antiaggregation activity (Arg-Gly-Asp, Lys-Gly-Asp and Pro-Gly-Pro) to a peptide mimicking the space structure of the α-helix B of erythropoietin pHBSP (Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser). Materials and methods: The cytoprotective activity of innovative peptides mimicking the space structure of the α-helix B of erythropoietin at the doses of 5 μg/ml, 30 μg/ml and 50 μg/ml was studied on human endothelial cell culture in a simulated oxidative stress. An ADMA-like model of preeclampsia was simulated in the experiment. The study was conducted in 260 female Wistar rats, weighing 250–300 g. Results and discussion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin retain their cytoprotective activity in a simulated oxidative stress in HUVEC cell culture at the doses of 5 μg/ml, 30 μg/ml, and 50 μg/ml. The compounds with laboratory codes P-αB1 and P-αB3 had the most pronounced cytoprotective activity. Administration of N-nitro-L-arginine-methyl ether to pregnant females for 7 days causes the morphofunctional changes similar to clinical changes in preeclampsia. The innovative peptide under laboratory code P-αB4 at the dose of 50 μg/kg mimicking the space structure of the α-helix B of erythropoietin shows the most pronounced protective properties. Conclusion: Innovative peptides mimicking the space structure of the α-helix B of erythropoietin have a pronounced positive influence on the morphofunctional disorders in animals with ADMA-like preeclampsia.

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