Introduction. The drugs affecting a mitochondrial dysfunction, oxidative stresses, apoptosis and inflammation of the vascular wall, have a high potential for the prevention and treatment of atherosclerotic lesions. In this regard, the use of EPOR/CD131 heteroreceptor agonists which have a similar spectrum of pharmacological effects, is one of the promising strategies in the treatment of cardiovascular diseases.Materials and Methods. The study was carried out on 68 C57Bl/6J male mice. Atherosclerosis was simulated in transgenic animals with an endotheliospecific knockdown of the Polg gene by simulating a balloon injury and keeping on a Western diet. Then, the studied drugs were injected once every 3 days at the dose of 20 μg/kg for 27 days. On the 28-th day, the animals were euthanized and the area of atherosclerotic plaques was assessed. The gene expression associated with the processes of inflammation, antioxidant protection, apoptosis, and angiogenesis was also determined in the aortic tissues. In addition, the endothelium protective effect of peptides on primary cultures of endothelial cells of wild and transgenic Polg-D257A mice was studied.Results. No statistically significant effect of drugs on the area of lipid infiltration have been found. However, the studied peptides have significantly reduced the expression of proinflammatory genes (iNos, Icam1, Vcam1, Sele, Il6, Tnfa), the genes associated with angiogenesis (Vegfa, Kdr, and Hif1a), the expression of proapoptic factors; they decreased the Bax/Bcl-2 ratio by more than 1.5 times. In addition, when supplemented with H2 O2  in vitro, peptides dose-dependently increased endothelial cell survival.Conclusion. The erythropoietin-based peptides can be used to improve the functional state of the vascular wall against the background of atherosclerotic lesions and have a depressing effect on pathobiological processes associated with a mitochondrial dysfunction. In addition, the studied peptides have a significant endothelial protective effect in the induction of oxidative stress in vitro.

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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Mitohondrial'naya disfunkciya yavlyaetsya klyuchevym drajverom razvitiya nejrodegeneracii. Cel'yu issledovaniya bylo ocenit' protektivnyj potencial stimulyacii EPOR/CD131, geterodimernogo receptora eritropoetina (EPO), pri nejrodegeneracii, vyzvannoj narusheniem funkcii mitohondrij. V kachestve agonistov EPOR/CD131 byli ispol'zovany EPO ili pHBSP, effektivnost' kotoryh ocenivali v usloviyah in vivo i in vitro. V modeli rotenon-inducirovannoj retinopatii odnokratnaya in"ekciya 10 mkg/kg EPO ili 5 mkg/kg pHBSP privela k znachitel'nomu snizheniyu degeneracii ganglionarnyh kletok setchatki (p < 0,05). Krome togo, inkubaciya v 500 nM rastvorah EPO i pHBSP rezko uvelichila vyzhivaemost' pervichnoj myshinoj nejroglial'noj kul'tury, obrabotannoj rotenonom (p < 0,005). Primechatel'no, chto primenenie agonistov EPOR/CD131 privelo k uvelicheniyu ekspressii mRNK LC3A, ATG7, Beclin-1, Parkina i BNIP3, chto svidetel'stvuet ob aktivacii autofagii i mitofagii kak potencial'nom mekhanizme mitoprotektivnogo dejstviya.

Povrezhdenie setchatki yavlyaetsya neklassicheskim simptomom ryada nejrodegenerativnyh zabolevanij, vklyuchaya bokovoj amiotroficheskij skleroz (BAS). Cel'yu raboty bylo ocenit' morfofunkcional'noe sostoyanie setchatki v myshinoj modeli BAS, svyazannoj s superekspressiej aberrantnogo belka FUS[1-359]. Issledovanie provodili na 12 transgennyh i 13 dikih myshah 2,5–3-mesyachnogo vozrasta. Vyyavleno, chto transgennye myshi demonstriruyut vyrazhennuyu, no ne dostigayushchuyu statisticheskoj znachimosti tendenciyu k razvitiyu oftal'moskopicheskih anomalij setchatki. Krome togo, molekulyarno-biologicheskij analiz podtverdil uvelichenie ekspressii provospalitel'nyh genov Vegfa, Il1b, Il6, Icam1, Tnfa. Pri etom, nesmotrya na obnaruzhennye strukturnye i funkcional'nye anomalii, vestern-blot analiz i kolichestvennaya PCR ne vyyavili ekspressiyu belkovogo i mRNK produkta transgena FUS v setchatke mutantnyh myshej.