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

• 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)