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

Abstract

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.

ACTH6-9-PGP improves memory consolidation processes in rats

“…These factors are known to affect the growth and differentiation of nerve cells, as wel as to stimulate the synthesis of various biologically active substances. In addition, neurotrophic factors, mainly BDNF (brain-derived neurotrophic factor), are involved in learning and the formation of a memory trace in the mammalian brain (Dolotov et al 2006;Dmitrieva et al 2010;Koroleva and Myasoedov 2018;Korokin et al 2019). It is important to note that the BDNF level significantly increases only 3 hours after the administration of ACTH analogs, in particular, ACTH 4-7 -PGP, which indicates its participation only in delayed mechanisms of memory formation, including the consolidation of the memory trace.…”

3D organotypic cell structures for drug development and Microorganism-Host interaction research

“…Most studies performed using microphysiological systems are aimed to study the toxicity of drugs, and only in some cases to identify their effectiveness (Denisuk et al 2015;Truskey 2018;Korokin et al 2019).…”

Study of Antiatherosclerotic and Endothelioprotective Activity of Peptide Agonists of Epor/Cd131 Heteroreceptor

“…Первым препаратом из данной группы был 11-аминокислотный пептид pHBSP (pyroglutamate helix B surface peptide), открытый в 2008 г. научной группой под руководством Майкла Брайнса [9]. Прежде мы продемонстрировали, что данный пептид оказывает выраженное эндотелиопротективное действие при моделировании L-NAME-индуцированной эндотелиальной дисфункции у крыс [10,11]. Однако в этом исследовании нами также был выявлен побочный эффект в виде протромботического действия.…”