Tag Archives: atherosclerosis
Protective action of N-stearoylethanolamine on blood coagulation and arterial changes in spontaneously hypertensive rats fed cholesterol-rich diet
O. S. Tkachenko1, Ie. A. Hudz1*, H. V. Kosiakova1,
P. P. Klymenko2, Y. M. Stohnii1, V. A. Didkivskyi1,
T. M. Chernyshenko1, V. O. Chernyshenko1, T. M. Platonova1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2SI “D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine”, Kyiv;
*e-mail: goudziegor@gmail.com
Received: 24 December 2019; Accepted: 27 March 2020
In this work we aimed to test the atherosclerotic changes in the aortic wall and pro-coagulant response of the blood coagulation system of spontaneously hypertensive rats (SHR) fed cholesterol-rich diet (CRD) and to study the effect of the anti-inflammatory agent N-stearoylethanolamine (NSE) on the development of atherosclerosis in this model. Female rats (n = 30) with genetically determined hypertension proven by direct measurement of blood pressure were fed CRD (5% cholesterol) for 2 months. Control group of SHR (n = 10) received standard pellet diet, 10 were fed CRD and 10 received CRD with daily per os application of NSE at a dose of 50 mg/kg of body weight. Histological analysis detected swelling and detachment of endothelial cells, huge edema of the subendothelial layer and a disruption of the middle shell integrity. CRD rats had higher fibrinogen concentration, increased rate of platelet aggregation and decreased level of anticoagulant PC. Platelet aggregation speed increased in CRD-fed rats (52.5±4.1%/min) was slightly normalized under the action of NSE (40±8.3 vs 35±9%/min in controls). Fibrinogen concentration was slightly increased in CRD-fed rats (2.75±0.7 vs 1.9±0.5 mg/ml in controls). However, the level of anticoagulant PC that was decreased in CRD-fed rats (65±16 vs 100±11% in controls) was normalized under the action of NSE (92±17%). NSE also influenced the aorta architecture, however normalizing the thickness of the aorticwall did not change the cholesterol-induced inclusions within aorta media. NSE anti-inflammatory action changes the atherogenic processes in CRD-fed rats mainly protecting PC from consumption during the inflammatory process and reducing edema of the aorta. However hematological parameters (including clotting time in the APTT test and fibrinogen concentration) changed independently on NSE application. Anti-aggregatory action of NSE on platelets can be a result of direct action on platelets or the consequence of its anti-inflammatory action. During atherogenesis induced by CRD in the model, NSE demonstrated valuable anti-inflammatory action protecting the organism during atherogenesis, however it cannot be assumed as an antithrombotic or antiatherogenic agent because it is unable to influence hemostasis directly.
Blood coagulation and aortic wall integrity in rats with obesity-induced insulin resistance
O. S. Dziuba1, V. O. Chernyshenko1, Ie. A. Hudz1, L. O. Kasatkina1, T. M. Chernyshenko1,
P. P. Klymenko2, H. V. Kosiakova1, T. M. Platonova1, N. M. Hula1, E. V. Lugovskoy1
1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: oksana.dziuba86@gmail.com;
2State Institute of Gerontology of AMS of Ukraine, Kyiv
Obesity is an important factor in pathogenesis of disorders caused by chronic inflammation. Diet-induced obesity leads to dyslipidemia and insulin resistance (IR) that in turn provoke the development of type 2 diabetes and cardiovascular diseases. Thus, the aim of this work was to investigate the possible pro-atherogenic effects in the blood coagulation system and aortic wall of rats with obesity-induced IR. The experimental model was induced by a 6-month high-fat diet (HFD) in white rats. Blood samples were collected from 7 control and 14 obese IR rats. Prothrombin time (PT) and partial activated thromboplastin time (APTT) were performed by standard methods using Coagulometer Solar СТ 2410. Fibrinogen concentration in the blood plasma was determined by the modified spectrophotometric method. Levels of protein C (PC), prothrombin and factor X were measured using specific chromogenic substrates and activating enzymes from snake venoms. Platelet aggregation was measured and their count determined using Aggregometer Solar AP2110. The aorta samples were stained by hematoxylin and eosin according to Ehrlich. Aortic wall thickness was measured using morphometric program Image J. Statistical analysis was performed using Mann-Whitney U Test. The haemostasis system was characterized by estimation of the levels of individual coagulation factors, anticoagulant system involvement and platelet reactivity. PT and APTT demonstrated that blood coagulation time strongly tended to decrease in obese IR rats in comparison to the control group. It was also detected that 30% of studied obese IR rats had decreased factor X level, 40% had decreased level of prothrombin whereas fibrinogen concentration was slightly increased up to 3 mg/ml in 37% of obese IR rats. A prominent decrease of anticoagulant PC in blood plasma of obese rats was detected. Obese IR rats also had increased platelet count and higher rate of platelet aggregation in comparison to control animals. Histological analysis identified the disruption of aorta endothelium and tendency for the thickening of the aorta wall in the group with obesity-induced IR compared to the group of control rats. Changes of individual coagulation factors were assumed as the evidence of imbalance in the blood coagulation system. Increase of fibrinogen level, drop in PC concentration and pathological platelet reactivity were taken to corroborate the development of low-grade inflammation in obese IR rats. Instant generation of small amounts of thrombin in their blood plasma is expected. Since the aorta morphology assay detected the trend of its wall to thicken and the emergence of disruptions, we assumed there were initial stages of atherosclerosis and the danger of developing atherothrombosis. We detected an increase of blood coagulability and changes in aorta morphology in rats with obesity-induced IR which we assume indicate early development of atherosclerosis.
Biological role of fetuin A and its potential importance for prediction of cardiovascular risk in patients with type 2 diabetes mellitus
M. Yu. Gorshunska1, Y. I. Karachentsev1,2, N. A. Kravchun2, E. Jansen3,
Zh. A. Leshchenko2, A. I. Gladkih2, N. S. Krasova2,
T. V. Tyzhnenko2, Y. A. Opaleyko2, V. V. Роltorak2
1Kharkiv Postgraduate Medical Academy,Ukraine;
2SI V. Danilevsky Institute of Endocrine Pathology Problems,
National Academy of Medical Sciences of Ukraine, Kharkiv;
3National Institute for Public Health and the Environment,
Bilthoven, Netherlands;
e-mail: maryanagr@mail.ru
The authors’ data and those from literature concerning biological role of fetuin A glycoprotein have been generalized in the article. A direct correlation has been established between fetuin A and some adipokines involved in the formation of insulin resistance and atherogenesis (progranulin, omentin-1), and osteoprotegerin (the novel cardiovascular risk factor) as well as an increase of circulating levels of fetuin A in patients with type 2 diabetes mellitus with high cardiovascular risk metabolic pattern but without manifestations of macrovascular complications. This substantiates the involvement of fetuin A in the complex of biomarkers of subclinical atherosclerosis.