Репозиторий Университета

© 2019, Spandidos Publications. All rights reserved. Adiponectin, endothelin and nitric oxide (NO) are major regulators of vascular function. An imbal-ance of vasoactive factors contributes to the onset and progression of atherosclerosis. Various single nucleotide polymorphisms (SNPs) are considered to be risk factors for coronary heart disease. However, the molecular mechanisms of their associations with the components of endothelial dysfunction are poorly understood. In the present study, rs17366743, rs17300539, rs266729, rs182052 and rs2241766 SNPs of the adiponectin (ADIPOQ) gene and rs2070699, rs1800542 and rs1800543 SNPs of the endothelin-1 (EDN1) gene were genotyped in 477 patients with coronary heart disease who were subjected to coronary angiography, in order to determine the presence or absence of coronary atherosclerosis. The serum levels of adiponectin, endothelin and stable metabolites of NO, (nitrate and nitrite NOx), were assayed and their associations with the SNP genotypes and coronary lesions were calculated. The results indicated that rs17366743 of the ADIPOQ gene and rs2070699 and rs1800543 of the EDN1 gene were associated with the levels of NOx in women, which in turn was associated with cardiovascular mortality. In men, rs182052 and rs266729 of the ADIPOQ gene were associated with adiponectin levels, whereas rs17366743 of the ADIPOQ gene was associated with endothelin levels. Additionally, these SNPs were indirectly associated with the prevalence of coronary lesions in men. Therefore, the tested SNPs can be considered potential risk factors that lead to imbalance of vasoactive mediators in a gender-specific manner and contribute to the development of clinical manifestations of atherosclerosis.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. The superficial femoral artery (SFA) is a typical atherosclerosis-prone site. We aimed to explore whether the tortuosity of the SFA associates with the occurrence of atherosclerosis and investigate how vascular tortuosity influences the characteristics of blood flow. Ten patients diagnosed with atherosclerotic disease in their SFAs while free of systemic atherosclerosis risk factors were enrolled together with ten atherosclerosis-free patients. The tortuosity of each SFA was quantitatively evaluated by calculating the averaged curvature (AC), maximum curvature (MC) and fraction of high curvature (FC) based on the geometrical model reconstructed from medical images. Hemodynamic studies were performed using both geometrically simplified and anatomically realistic models of the SFA to systematically address the hemodynamic effects of vascular tortuosity. Morphological analyses revealed that all curvature indices of the SFA were significantly larger in patients with atherosclerosis than in atherosclerosis-free patients (AC [mm−1]: 0.034 ± 0.016 vs. 0.018 ± 0.006; MC [mm−1]: 0.055 ± 0.023 vs. 0.034 ± 0.008; FC [%]: 22.77 ± 10.22 vs. 11.39 ± 6.82; p < 0.001). Simulations of blood flows in the geometrically simplified SFAs showed that increasing vascular curvature caused a progressive increase in the area ratios of low wall shear stress (LWSA) and high oscillatory shear index (HOSA). Hemodynamic studies on the anatomically realistic SFAs further demonstrated that high-curvature SFAs (n = 10) had overall larger LWSA and HOSA compared with low-curvature SFAs (n = 10) (LWSA [%]: 4.13 ± 1.91 vs. 1.79 ± 1.13, p = 0.009; HOSA [%]: 4.95 ± 1.92 vs. 2.37 ± 1.51, p = 0.007). These results suggest that increased vascular tortuosity augments the severity and distribution of atherosclerosis-promoting flow disturbances in the SFA and may be an independent risk factor for atherosclerosis.

The atherosclerosis is considered among the most prevalent diseases. In Russia, N. N. Anitchkov and A. L. Miasnikov are founders of atherosclerosis studies. Valentina Iosifovna Miasnikova, doctor of medical sciences, professor of the Chair of Faculty Therapy #2 of the Sechenov University is one the numerous followers of A. L. Miasnikov. From the early 1960s, Valentina Iosifovna, proceeding with ideas of N. N. Anitchkov and A. L. Miasnikov, actively investigated pathogenesis of atherosclerosis. The professor V. I. Kalmykova, one of the first in Russia presented pathogenesis of atherosclerosis as a multi-factorial process and, combining theories existed at that moment, described effect of peroxidation of lipids on all stages of development of atherosclerotic plaque. She carried out a unique scientific investigation concerning studying intensity of peroxidation of lipids and antioxidant activity of lipids in patients with various degree of expression of ischemic heart disease. The gender characteristics of content of peroxides and antioxidant activity of lipids of blood serum were established. The research works of professor V. I. Kalmykova made an invaluable contribution into comprehension of pathogenesis of atherosclerosis and obtained an international approval. The scientific data obtained by V. I. Kalmykova were confirmed by studies of national and international researchers. Nowadays, the role of oxidation process in pathogenesis of atherosclerosis and ischemic heart disease is generally acknowledged.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Mainly, intracoronary thrombosis is the cause of acute coronary syndrome. The structure of the atherosclerotic plaque plays an important role in the development of the mechanism of intracoronary thrombosis. Currently, there are various radiological methods for diagnosis of atherosclerotic plaques of the coronary arteries. The current review reveals the theme of "indirect" signs of instability of atherosclerotic plaques, their combinations and occurrence, detected by computed tomography. Retrospective studies have shown the feasibility of these signs of plaques in the assessment of the prognosis of acute coronary events. The review compares the results of computed tomography (CT) and intravascular ultrasound, which is the gold standard in the diagnosis of atherosclerotic plaque morphology.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Aim. Determination of desialized apolipoprotein-B-100 (apoB-100) and lipoprotein-containing circulating immune complexes in patients with chronic kidney disease (CKD) in program hemodialysis with type 2 diabetes mellitus. Materials and methods. We examined 81 patients with CKD (50 men / 31 women) treated with program hemodialysis, of which 36 (17/19) with type 2 diabetes mellitus, 45 (33/12) non-diabetic patients. The levels of total cholesterol, triglycerides and desialylated apoB-100 in blood plasma and lipoprotein-containing circulating immune complexes. A color duplex scan of brachiocephalic arteries was used to assess the extent of development of atherosclerosis with the determination of the thickness of the intima-medial complex. Results and discussion. Patients with diabetes had high values of total cholesterol, triglycerides (p<0.05). Duplex scan of brachiocephalic arteries showed an increase in the thickness of intima-medial complex in all patients for program hemodialysis, however, in patients with diabetes, the thickness was 13% higher (p<0.05). In patients with diabetes, plaques with stenosis up to 50% prevail, compared with non-diabetic patients, p<0.05. The incidence was significantly higher for desialized apoB-100 by 46% in patients with diabetes on hemodialysis compared non-diabetic patients (p<0.05). An increase in the level of lipoprotein-containing circulating immune complexes by 39%, (p<0.05) in patients with diabetes mellitus was observed, compared with patients non-diabetic patients. The correlation between desialized apoB-100 and duplex scan of brachiocephalic arteries parameters (r=0.325), as well as between the cholesterol level and stenosis up to 50% (r=0.465) in patients with diabetes mellitus, was found to be of medium strength. The patients with diabetes and CKD, myocardial infarction developed 79% more often than in patients without diabetes (p<0.05). Thus, immunogenic lipid markers of atherosclerosis can be considered both as mechanical factors of atherogenesis and diagnostic and prognostic characteristics in type 2 diabetic patients with impaired renal function and chronic renal insufficiency. The conclusion. Accelerated development of atherosclerosis with diabetes and CKD, confirmed with the help of duplex scan of brachiocephalic arteries, may be associated with an increase in the level of modified low density lipoprotein.

© 2018, Media Sphera Publishing Group. All rights reserved. The paper describes the procedure to prepare endothelial cell monolayer samples from the vascular intima, which is suitable for studying various morphological processes. To obtain high-quality multicellular specimens, it is recommended to preliminarily remove excess tissue from the outside of the vessel and to free the intima; ways to dry the surface and to separate endothelial cells are examined. The paper gives the figures of specimens stained by the Romanowsky-Giemsa method and identifies factor VIII, an endothelial marker, and Chlamydia pneumoniae inclusions in the cytoplasm of endothelial cells.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Vitamin D deficiency is widespread worldwide and present in about 30-50% of population. In most cases, this problem is associated with musculoskeletal system pathology: Rickets in children, and osteomalacia or osteoporosis in adults. However, in recent years, convincing data was obtained on the links between Vitamin D deficiency and cardiovascular pathology. Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe cardiovascular diseases, including strokes and infarctions. It has been demonstrated that Vitamin D has a strong vasoptotective effect via endothelial dysfunction improvement, prevents blood vessels and myocardium remodeling, improves blood pressure parameters, reduces the risk of development of left ventricular hypertrophy, slows down fibrosis, reduces the risk of atherosclerosis, reduces insulin resistance, and also affects inflammation and immunity. This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic heart failure.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. The purpose of this study is to compare the diagnostic performance of coronary computed tomographic angiography (CCTA) and stress test as a first-line examination for the diagnosis of stable coronary artery disease in outpatient settings. Materials and methods. The study prospectively enrolled 74 patients with typical and atypical angina symptoms lasting longer than three weeks, mean age-63,9±10,4 years, 28 (37,8%) women. Exclusion criteria: contraindications to iodine-containing contrast media, statins; GFR <45ml/min/1,73 sq m; inability to perform stress testing. All patients consistently underwent stress testing (standard Bruce protocol and The Modified Bruce protocol) and standard CCTA on a 640-slice CT scanner Toshiba Aquilion ONE. We determined pretest probability of CAD and stratified risks using SCORE and ACC/AHA scales. Statistical processing was performed with SPSS version 11,5 software. Results. Treadmill test results were positive in 51,4% of patients, among them according to CCTA: 19,15% had stenosis = 70%, 35,3% had stenosis 50-69%. CCTA revealed that 28,6% of males and 46,2% of females with typical and 66,7% of males and 50,0% of females with atypical angina symptoms with positive treadmill test had no evidence of atherosclerotic lesions. 4,05% of patients with negative stress testing had evidence of significant arterial lesions (stenosis >70%). According to the SCORE risk estimation, 67,6% of patients with atherosclerotic changes in coronary arteries had high risk, ACC/AHA score-70,6%. The sensitivity and specificity of the SCORE and ACC/AHA scales in revealing coronary atherosclerosis were 83% and 71%, 81% and 88%, respectively (p> 0.05). Conclusion. CCTA can be considered as a method for the primary diagnosis of stable coronary artery disease in outpatient practice.

© 2018 Media Sphera Publishing Group. All rights reserved. According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CÀNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative antiinflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

© 2018 Media Sphera Publishing Group. All rights reserved. The article presents a clinical observation of two patients with generalized sarcoidosis. The woman typical granulomatous changes in the lungs and lymph nodes combined with atrial fibrillation, kidney failure and hereditary thrombophilia, men with atherosclerotic coronary arteries, re-myocardial infarction, cholestasis, tubulointerstitial nephritis. The accession of systemic manifestations was accompanied by increase of level of angiotensin-converting enzyme in the blood serum, morphological examination of lung tissue in both cases there were high histological activity of vasculitis and granulomatous inflammation. Extrapulmonary symptoms regressed when conducting immuno-suppressive therapy. Discusses modern aspects of diagnosis of sarcoidosis in clinical practice.

© 2018 Ima-Press Publishing House. All rights reserved. Atherosclerosis is now considered as chronic inflammatory vascular disease connected to «pathological» activation of innate and adaptive immunity, characterized by lipid deposition, leukocyte infiltration and proliferation of vascular smooth muscle cells. Subclinical (low grade) inflammation plays fundamental role at all stages of atherosclerotic process progression and determines cardiovascular catastrophes development and mortality. Proinflammatory cytokines including interleukin (IL) 1, IL6, tumor necrosis factor α (TNFα), IL17, IL18, IL27, IL33, IL37 tightly interacting within cytokine network occupy an important place among numerous mediators participating in immunopathogenesis of atherosclerosis and rheumatoid arthritis. IL1β playing an important role in the development of many acute and chronic immunoinflammatory diseases attracts particular attention. IL1β significance in the development of atherosclerosis is determined by many mechanisms including procoagulant activity, enhancement of monocytes and leucocytes adhesion to vascular endothelium, vascular smooth muscle cells growth and others. Fundamental role of inflammation in the development of atherosclerosis is well proved in investigations of anti-atherosclerotic effect of canakinumab. Randomized placebo-controlled trial CANTOS (Canakinumab ANti-inflammatory Thrombosis Otcomes Study) assessing efficacy of canakinumab as new tool for secondary prophylaxis cardiovascular complications in general population of patients with severe atherosclerotic vascular damage. CANTOS results in combination with accumulated in rheumatology data on cardiovascular effects of anti-inflammatory drugs are of great importance for personification of approach to secondary prophylaxis of caused by atherosclerosis cardiovascular complications. They also contribute to the development of inflammatory theory of atherosclerosis pathogenesis in the whole.

© 2018 Stolichnaya Izdatelskaya Kompaniya. The review focuses on the impairment of the carotid, coronary arteries and lower-extremity arterial disease. Systemic involvement of various vascular beds in atherogenesis is emphasized. Epidemiological characteristics of morbidity and mortality from the main clinical manifestations of atherosclerosis - ischemic stroke, ischemic heart disease and lower-extremity arterial disease are given. The current principles of drug therapy are considered from the point of view of improving the prognosis and eliminating ischemia. The basic positions of International and Russian clinical recommendations on the management of patients with the presence of certain clinical manifestations of atherosclerosis are discussed. Detailed administration schemes and the preferred doses of statins and antiplatelet agents depending on the localization of atherosclerotic lesion and the severity of stenosis are described. The target blood lipids levels in the treatment with statins are given. The advantages of statins as drugs that reduce the risk of cardiovascular complications are presented. Current data on the pattern of antiplatelet use, including acetylsalicylic acid, in individuals with clinical manifestations of atherosclerosis are given. The principal tactic of dual antiplatelet therapy and schemes of its use in patients undergoing percutaneous coronary intervention, coronary artery bypass surgery and in individuals with a history of acute coronary disorders are considered..

© 2018 Bentham Science Publishers. Background: This study discusses the crucial factors responsible for the progression of atherosclerotic cardiovascular disease (CVD). The interaction between the gut microbiota, heart and vessels in CVD pathogenesis is extremely complex and includes components such as direct bacterial translocation from the gut to vessels and metabolitemediated damage. To a greater extent, CVD seems to be entangled with a subtle immune system-to-microbiota interface. From among the most significant advances in recent years in this area, it is necessary to highlight the discovery of the pro-atherogenic effect of trimethylamine-N-oxide (TMAO) and changes in the activity of effector T-cells in the settings of dysbiosis. Currently, we are witnessing an explosive growth in interest in using the microbiota and interlinked cascades as a target for therapeutic interventions, including direct microbiome targeting, the attenuation of toxic metabolite-induced damage, the modulation of intestinal immunity, and downstream inhibition of systemic inflammatory pathways. Objective: In this brief review, modern strategies of microbiome-based therapies for the prevention and treatment of CVD are classified and discussed from the perspective of personalized medicine.

AIM: To study the state of cerebral hemodynamics and platelet hemostasis in patients with carotid stenosis (CS). MATERIAL AND METHODS: The prospective study included 123 patients with atherosclerotic CS. The 1st group included 53 patients (mean age 52±12.5 yrs) who underwent carotid endarterectomy (CEA); the 2nd group - 70 patients who were treated conservatively (mean age 58.5±15.9 yrs). The state of blood flow through the main arteries of the head (Doppler flowmetry), platelet aggregation induced by adrenaline, the frequency of acute cardiovascular events that occurred during 12 months were evaluated. RESULTS AND CONCLUSION: The severity of neurological deficits and cognitive impairment increased with increasing of the degree of CS. CEA leads to an improvement of cerebral hemodynamics and stabilization of cognitive functions. The adverse course of the disease occurred in 23.6% of patients (stroke/heart attack during the year in 5.7%, progression of cerebral ischemia in 20%, restenosis within 5 years after CEA in 15%). Hyperaggregation of platelets induced by ADP and epinephrine and decreased aggregation of platelets induced by collagen in patients receiving ASA were identified in 53% of the operated and in 60% of non-operated patients. The use of combined antiplatelet therapy normalize the platelet hemostasis and reduce the frequency of acute cardiovascular events.

© 2018 Media Sphera Publishing Group. All rights reserved. Prolyl-4-hydroxylases of hypoxia-inducible factor (HIF-P4Hs) are enzymes that, under the conditions of normoxia, cause degradation of the HIF-transcriptional protein, which regulates a number of metabolic processes, including erythropoiesis, glucose level and lipid metabolism. In hypoxic conditions, on the contrary, their activity is suppressed and HIF stabilization takes place. This mechanism, i.e. stabilization of HIF by inhibition of HIF-P4Hs was the basis for the development of drugs designed for treatment of renal anemia, which are currently in stages 2 and 3 of clinical trials and are showing encouraging results. Recently, it has also been reported that inhibition of HIF-P4Hs can be effective in treatment of cardiometabolic diseases - coronary heart disease, hypertension, obesity, metabolic syndrome, diabetic cardiomyopathy and atherosclerosis. The review, based on the most recent data, discusses in detail molecular mechanisms of therapeutic effect of HIF-P4Hs inhibition in these pathological conditions and provides evidence that these mechanisms are associated with HIF stabilization and gene expression, improving perfusion and endothelial function, reprogramming metabolism from oxidative phosphorylation to anaerobic glycolysis, reducing inflammation and having beneficial effect on the innate immune system.