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

Artikel i vetenskaplig tidskrift
Författare M. V. Korokin
V. O. Soldatov
Alesia A. Tietze
I. V. Golubev
A. E. Belykh
M. V. Kubekina
O. A. Puchenkova
T. A. Denisyuk
V. V. Gureyev
T. G. Pokrovskaya
O. S. Gudyrev
M. A. Zhuchenko
M. A. Zatolokina
M. V. Pokrovskiy
Publicerad i Farmatsiya i Farmakologiya
Volym 7
Nummer/häfte 6
Sidor 312-320
ISSN 2307-9266
Publiceringsår 2019
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 312-320
Språk en
Länkar dx.doi.org/10.19163/2307-9266-2019-...
Ämnesord Atherosclerosis, Cibenitide, Endothelium, Erythropoietin, P-αB, Rats, acetylcholine, alpha helix of B erythropoietin, amino acid derivative, endothelial nitric oxide synthase, interleukin 1beta, messenger RNA, n(g) nitroarginine methyl ester, nitroprusside sodium, tumor necrosis factor, unclassified drug, abdominal aorta, abdominal aortic wall, alpha helix, animal cell, animal experiment, animal model, animal tissue, aortic tissue, Article, blood pressure monitoring, blood vessel function, carotid artery thrombosis, controlled study, diastolic blood pressure, endothelial dysfunction, ferric chloride-induced thrombosis, histology, L-NAME-induced hypertension, male, nonhuman, protein expression, protein expression level, protein structure, rat, real time polymerase chain reaction, systolic blood pressure, thrombogenicity, thrombosis, vascular endothelium, vasodilatation
Ämneskategorier Biokemi och molekylärbiologi

Sammanfattning

An 11-amino acid peptide imitating the natural structure of B erythropoietin α-helix (P-αB), has a specific affinity to the heterodimeric complex EPOR/CD131. 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. The results 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. © 2019 Volgograd State Medical University, Pyatigorsk Medical and Pharmaceutical Institute. All rights reserved.

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