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AIM: To evaluate the level and activity of von Willebrand factor (vWF) in patients with peripheral artery disease (PAD) who underwent endovascular or open bypass grafting. MATERIAL AND METHODS : The study included 115 patients with chronic lower limb ischemia due to PAD, stage IIb-IV according to A.V. Pokrovsky–Fontaine. Fifty-five participants underwent endovascular treatment, while sixty underwent open bypass procedures using synthetic grafts. Peripheral blood samples were collected from all patients at baseline and three months after invasive treatment to determine the vWF antigen and activity. All patients were monitored every three months for a year to detect the development of unfavorable outcomes including disease progression, restenosis, graft thrombosis, oncology, myocardial infarction (MI), limb loss, stroke, and lethal outcomes. RESULTS : The highest values of vWF antigen in patients who underwent endovascular treatment were detected in patients with multilevel lesions–1.25 µg/mL (vs 0.2 µg/mL, 95% confidence interval (CI) 0.72–3.21 mcg/mL p = 0.019); with a similar trend observed after a 3–month follow-up. Baseline vWF antigen was higher in endovascular group patients who developed myocardial infarction (MI) within a year following the procedures as compared to those without MI: 1.15 mcg/mL (95% CI 1.05–1.175 mcg/mL) and 0.9 mcg/mL (95% CI 0.78–1.01 mcg/mL), respectively (p = 0.015). Moreover, vWF antigen was increased at the 3-month follow-up in patients with lethal outcomes–1.06 mcg/mL (95% CI 0.96–1.18 mcg/mL, р = 0.031). vWF activity in endovascular group patients with developed MI was four times higher than those without MI (р = 0.022); a similar trend was detected in the development of lethal outcomes (р = 0.009). Those who underwent open bypass grafting presented with high activity of vWF with maximum values detected in participants with proximal iliofemoral lesions (1200%, 95% CI 640%–1200%) and stage IV disease (770%, 95% CI 320%–1200%, p < 0.05). ROC analysis revealed that vWF activity at least 6.2 times higher in patients who underwent endovascular treatment associated with the development of lethal outcomes within one year after invasive treatments; sensitivity and specificity of the method were 83.3% and 75.5%, accordingly. CONCLUSION : Patients with PAD presented with increased vWF antigen and activity with maximum values detected in patients with multilevel lesions and critical lower limb ischemia. Increased vWF antigen and activity was associated with development of MI and lethal outcomes within one year following endovascular procedures on lower extremity arteries.

Dysferlin is a transmembrane calcium-binding protein of the ferlin-1-like protein family, which includes myoferlin Fer1L3, otoferlin Fer1L2 and other ferlins Fer1L4, Fer1L5, and Fer1L6 along with dysferlin itself. Dysferlin is synthesized in all cells of the body, but most actively – in the symplasts of striated muscle tissue. The full range of functions performed by this protein is not fully clarified, but the following have been clearly shown: participation in the post-injury repair of sarcolemma and intracellular vesicular systems, generation and maintenance of the correct functioning of the sarcolemmal T-tubule system, regulation of endo- and exocytosis and inflammation, participation in phagocytosis. Mutations in the dysferlin gene lead to the development of a number of neuromuscular diseases of the autosomal recessive type of inheritance called dysferlinopathies: Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, and distal anterior compartment myopathy. These diseases are characterized by the impaired expression of mRNA and/or the function of the protein dysferlin in skeletal muscles, which is caused by mutations in the DYSF (dystrophy-associated fer-1-like) gene. Although rare, dysferlinopathy is characterized by continuous progression causing severe disability, which explains the importance of research and development of appropriate treatments, including gene therapy. The article presents information on the structure of dysferlin, the mechanisms of its normal functions, as well as the biochemical basis of the pathogenesis of dysferlinopathies.

We studied the effect of nitinol, the most prevalent material for endovascular stents, on metabolic and coagulation activity of a primary culture of human umbilical vein endothelial cells (HUVEC). Metabolic activity was evaluated using MTS-test and by the level of stable NO metabolites in the conditioned medium, coagulation activity was assessed by activity of von Willebrand factor (vWF) and levels of plasminogen activator inhibitor-1 (PAI-1) and soluble endothelial protein C receptors (sEPCR). Exposure to nitinol reduced metabolic activity of the cell culture by 11.1% in comparison with the control (p

Varicose disease is the most prevalent vascular disorder affecting lower extremities. Chronic venous insufficiency (CVI) is common in subjects with incompetent superficial and perforator veins. Major attention in pathogenesis of CVI is paid to horizontal venous reflux, while pathological blood flow in the superficial veins may sometimes be regarded as a postural reaction. At the same time cardiac pathology may also attribute to the development of CVI. The article presents a case report describing a female patient with combination of the right heart pathology and varicose disease associated with tricuspid regurgitation leading to constant venous reflux in the lower extremity superficial veins with further development of trophic changes.

Aim . To study and compare cytotoxicity of the main types of synthetic prostheses used in arterial reconstructive surgery, including polytetrafluoroethylene (PTFE) and polyethylene-terephthalate (Dacron). Materials and Methods . On the culture of human umbilical vein endothelial cells (HUVEC) of the 3 rd passage, MTS test was conducted that is used in laboratory examinations with attraction of cellular technologies to study cytotoxicity of medical drugs and medical products. The test implies use of MTS reagent that is 3-(4,5-dimethylthiazol-2-il)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium; additionally phenazine methosulfate (PMS) was used that plays the role of electron-binding reagent. In the experiment, cells were incubated with PTFE and Dacron within 24 hours at 37ᵒC with 5% CO 2 . For control, HUVEC cultured in the standard growth medium, were used. In the presence of PMS, MTS was reduced by mitochondrial dehydrogenases of endothelial cells to formazan staining blue. Supernatant of cell cultures was evaluated by photocolorimetric method on Stat Fax 3200 analyzer (microplate reader) of Awareness technology Inc. Palm City Fl. (USA). Results . The lowest mean values were noted in Dacron group – 0.21 (0.20-0.22) optical density units, the highest values were noted in the control group – 0.36 (0.35-0.38); parameters in PTFE group were 0.35 (0.33-0.36). In comparison of the groups statistically significant differences were found between the control group and Dacron group (р

BACKGROUND: The syndrome of diabetic foot remains the main cause of non-traumatic amputation of the lower extremity in the world. Even with the provision of comprehensive medical care in the conditions of a specialized center, 10-15% of patients do not succeed in healing the ulcerative defect due to the ischemic component. AIMS: The objective of this study is evaluation of safety and efficacy of pl-VEGF165 transfer in patients with neuroischemic type of diabetic foot syndrome. METHODS: The pilot study included 35 diabetic patients with neuroischemic foot ulcers (Wagner stage 1-2) who were not candidates for revascularization procedures (NCT02538705). The patients were closely monitored after repeated pl-VEGF165 intramuscular gene transfer (2,4 mg) at 1, 3, and 6 months after treatment. The primary efficacy endpoint was the surface area of the ulcers (sq.cm), the secondary endpoints were transcutaneous oxygen tension (Tcp02), ankle-brachial index (ABI), neuropathy disability score (NDS), neuropathy symptoms score (NSS), and Michigan neuropathy screening instrument (MNSI). Adverse events were monitored throughout the study. RESULTS: The use of pl-VEGF165 as part of complex treatment allowed to achieve wound healing in 65,7% of patients with chronic ulcerative defects, the safety of the target limb was 84%. Carrying out therapeutic angiogenesis as a part of the combined therapy ensured a reduction in the average area of the resistant to treatment defects from 3.6 [1.0; 7.05] cm2 to 0.0 [0.0;2.0] cm2 (p=0,001), which correlated with an increase in the TcPo2 index by 15% from 35 [29.5; 40.5] to 40.5 [36.0; 46.5] mm Hg (p= p=0,005) and in the ABI by 16% from 0.96 [0.82;1.08] to 1.11 [0.85; 1.24] (p=0,062). The decrease in the signs of diabetic neuropathy was determined - the scores of NSS scales and VAT decreased from 6,5 [5.75; 8.0) to 6.0 [5.25; 7.0] (p=0,004) and from 9.0 [8.0; 13.5] to 8.0 [7.0; 12.7] (p=0,001), respectively. No adverse effects associated with the use of pl-VEGF165 were recorded. CONCLUSIONS: Thus, preliminary results of the pilot study show that the use of pl-VEGF165 gene transfer in combination therapy allows for complete healing of neuroischemic diabetic foot ulcers in the majority of patients.

Purpose: We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD). Materials and Methods : : This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed. Results : : At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (PConclusion : : Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis.

The number of patients receiving maintenance dialysis treatment has been growing in recent years. Unfortunately, the lifetime of PVA is not unlimited, and some patients initially have problems with its formation. Because of these problems, there is a need to develop new methods of forming constant vascular access in this cohort of patients. This case shows the successful surgical approach to forming permanent vascular access in patients who are intravenous drug users and who have post-thrombotic syndrome of most veins, making them unsuitable for creating an arteriovenous fistula.

Endothelial dysfunction is universally regarded as one of the key elements in the pathogenesis of most of cardiovascular diseases including ischemic heart disease, atherosclerosis, arterial hypertension, myocardial infarction, stroke, dilated cardiomyopathy, as well as diabetes mellitus, inflammatory, oncological, and autoimmune diseases. Localization of endothelial cells in tunica intima of the vessels limits in vivo analysis of the intracellular proteins and other molecules, which regulate cellular functional activity. A possible solution to this problem may be setting experimental conditions for physiological and pathological functioning of endothelial cells. In vitro modeling of endothelial dysfunction may be a useful tool for the development of methods to improve the endothelial function and evaluate the effects of medicinal products. The objective of this literature review is to summarize main trends in studying endothelial dysfunction in vitro using different endothelial cell cultures.

Lower extremity chronic venous disease is a highly prevalent vascular pathology. Progression of the disease exerts a negative impact on the patients' quality of life and imposes a large economic burden on the healthcare systems. Conventional methods of conservative treatment of chronic venous disease include wearing compression knitwear and pharmacological therapy. Although highly effective, compression therapy appears to be associated with lower compliance due to difficulties putting on and taking off the compression stockings. Therefore, the majority of patients prefer pharmacological therapy with phlebotonic drugs. There are many phlebotropic agents possessing particular indications and recommendations regarding the duration of administration. This article presents a review of the available literature addressing the problems related to prescription of pharmacotherapy to patients with lower limb chronic venous disease, also describing the results of published clinical studies evaluating efficacy and safety of phlebotropic drugs, as well as those concerning the duration of the course administration of drugs depending on the severity of the disease, invasive nature of a surgical intervention performed, or sclerotherapy. Besides, analysed is the role of phleboactive agents in correction of pathophysiological mechanisms of the development and progression of venous disease. This is followed by a review of clinical trials studying the influence of phlebotonics on such links of pathogenesis as leukocyte activation, vein-specific inflammation, endothelial dysfunction, and activation of proteolytic enzymes promoting destruction of the extracellular matrix. Based on the above data, proposed herein are appropriate approaches to determining the duration of the courses of phlebotropic therapy with due regard for the patients' status, underlying once again the importance and necessity of a personalized approach to selection of the optimal duration of venotonic therapy.Хронические заболевания вен нижних конечностей представляют собой самую распространенную патологию сосудов. Прогрессирование данных заболеваний оказывает негативное влияние на пациентов, а также ведет к большим экономическим затратам со стороны системы здравоохранения. К стандартным методам консервативного лечения хронических заболеваний вен относят использование компрессионного трикотажа и фармакологическую терапию. Несмотря на эффективность компрессионной терапии, у пациентов возникают определенные сложности с повседневным использованием трикотажа, что ведет к низкой приверженности данному методу лечения, поэтому большинство пациентов выбирают фармакологическую терапию. Существует множество флеботропных препаратов, имеющих определенные показания и рекомендации по длительности приема. В статье представлен обзор литературы, в котором рассматриваются вопросы назначения фармакотерапии пациентам с хроническими заболеваниями вен нижних конечностей. Приводятся литературные данные по клиническим исследованиям эффективности и безопасности флеботропных препаратов. Освещаются вопросы длительности курсового приема венотонизирующих препаратов в зависимости от клинических классов заболеваний, а также при проведении оперативных вмешательств и склеротерапии. Проанализирована роль флебопротекторов в коррекции патофизиологических механизмов формирования и прогрессирования заболеваний вен. Проведен обзор клинических исследований веноактивных препаратов на такие звенья патогенеза, как активация лейкоцитов, веноспецифическое воспаление, эндотелиальная дисфункция и активация протеолитических ферментов, способствующих разрушению внеклеточного матрикса. На основании представленных данных предложены подходы к определению длительности курсов флеботропной терапии, учитывая статус пациентов. В статье подчеркиваются важность и необходимость персонализированного подхода к выбору оптимальной продолжительности венотонизирующей терапии.

Background: The effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression, and new treatment methods are needed. In 2011, a plasmid VEGF65-gene therapy drug was approved in Russia for the treatment of chronic lower limb ischemia ( ClinicalTrials.gov identifier: NCT03068585). The objective of this follow-up study was to evaluate the long-term safety and efficacy of gene therapy in patients with limb ischemia of atherosclerotic genesis. Aims: To evaluate the long-term safety and efficacy of the therapeutic angiogenesis, 36 patients in the treatment group (pl- VEGF165) and 12 patients in the control group participated in a 5-year follow-up study. Planned examinations were carried out annually for 5 years after pl- VEGF165 administration. Results: Differences in the frequency of major cardiovascular events (pl- VEGF165 5/36 versus control 2/12; p = 0.85), malignancies (pl- VEGF165 1/36 versus control 0/12; p = 0.38) and impaired vision (there was none in either group) over the 5-year follow-up period did not achieve statistical significance. The target limb salvage was 95% ( n = 36) and 67% ( n = 12) in the pl- VEGF165 and control groups, respectively. The pain-free walking distance value increased by 288% from 105.7 ± 16.5 m to 384 ± 39 m in the treatment group by the end of the fifth year, with a peak of 410.6 ± 86.1 m achieved by the end of the third year. The ankle-brachial index (ABI) increased from 0.47 ± 0.01 to 0.56 ± 0.02 by the end of the first year, with a subsequent slight decrease to 0.51 ± 0.02 by the fifth year. The maximum increment of transcutaneous oximetry test (tcoO2) by 36%, from 66.6 ± 3.7 mm Hg to 90.7 ± 4.9 mm Hg, was observed by the end of the second year. Conclusion: The therapeutic effect of angiogenesis induction by gene therapy persists for 5 years.

We present a case of a 64-year-old woman with signs of debilitating condition including anginal chest pain, exertional dyspnea, and depression. The patient had previously suffered from a myocardial infarction after a loss of a close family member. Workup showed a posterobasal left ventricular aneurysm and moderate to severe mitral regurgitation in the absence of coronary atherosclerosis. Routine ultrasonography revealed abdominal aortic aneurysm and intraabdominal aortic deviation. The patient was immediately started on optimal medical treatment. On repeat assessment general condition was satisfactory, vital signs were normal, and investigations showed no signs of progressive heart failure or other significant clinical changes. Although prognosis in patients with myocardial infarction with normal coronary arteries is generally considered favorable, mechanical complications such as posterobasal left ventricular aneurysm with moderate to severe mitral regurgitation are possible.

Treatment options in patients with complete congenital heart block (atrioventricular block of III degree) may be controversial. Major obstacles are faced in pregnant women with newly detected heart block. Type of arrhythmia, presence of hemodynamic instability or syncope, anatomy of heart chambers and vessels, gestational age significantly influence the treatment. This article presents substantial information on etiology, pathogenesis, diagnostics, and possible treatment options in pregnant women with complete congenital heart block.

The protocols of performing treadmill tests (TMT) in patients presenting with peripheral artery disease have over the last decades undergone significant changes, with the alterations concerning not only the speed and time values of the load, but also the parameters measured. Currently, there is no unified generally accepted method of TMT, hence the need for an optimal protocol for carrying out this type of examination, which would help obtain reliable results in assessment of everyday life functional activity of patients and efficacy of various methods of treatment for peripheral atherosclerosis. The choice of an optimal methodology of performing a TMT in patients with intermittent claudication is extremely important because studying the haemodynamic parameters alone not always clearly reflect functional peculiarities of the course of the disease, since they depend not only on the presence of arterial stenoses or occlusions, but also on the activity of oxidative enzymes, endothelial and mitochondrial dysfunction, taking therapeutic agents, concomitant pathology and a series of other factors. The article is a review of the related literature contained in such databases as the Medline, PubMed, Russian Science Citation Index (RSCI) and Scopus and concerning TMT in patients with peripheral artery disease. The authors summarized the information from a total of 63 literature sources over the period from the 1970s to 2018.В течение последних десятилетий протоколы выполнения тредмил тестирования (ТМТ) у пациентов с заболеваниями периферических артерий претерпели существенные изменения: менялись как скоростные и временные параметры нагрузки, так и сами изучаемые показатели. Единого общепринятого метода ТМТ в настоящее время нет, в связи с чем требуется оптимальный протокол для выполнения данного вида исследования, что поможет получать достоверные результаты в оценке повседневной функциональной активности больных и эффективности различных методов лечения периферического атеросклероза. Выбор оптимальной методики выполнения ТМТ у пациентов с перемежающейся хромотой крайне важен в связи с тем, что исследования только гемодинамических показателей не всегда четко отражают функциональные особенности течения заболевания, так как последние зависят не только от наличия артериальных стенозов либо окклюзий, но и активности оксидативных ферментов, эндотелиальной и митохондриальной дисфункции, приема лекарственных препаратов, сопутствующей патологии и ряда прочих факторов. В обзоре представлены имеющиеся в базах Medline, PubMed, РИНЦ, Scopus литературные данные относительно ТМТ у пациентов с заболеваниями периферических артерий. Обобщена основная информация, представленная в 63 источниках литературы, за период с 1970-х гг. по 2018 г.

The combination of peripheral atherosclerosis and diabetes mellitus is a severe pathology, characterized by a high rate, mortality and social significance. The results of limb salvage and distant survival in this pathology in a remote period are unsatisfactory in spite of all existing treatment methods. Clinical trials in previous years have shown efficacy and safety of the medication, which is a plasmid construct with the gene encoding vascular endothelial growth factor - kambiogenplasmid, in patients with disease stage IIa-III according to the A.V. Pokrovsky and Fontaine classification, who were not indicated for surgical treatment. The article presents the clinical cases of successful use of this drug for therapeutic angiogenesis in patients with critical limb ischemia and severe type 2 diabetes mellitus. The inclusion of therapeutic angiogenesis in the conservative treatment algorithms is promising for the treatment of this group of patients. There is a need for further research on the efficacy and safety of the medication in patients with peripheral atherosclerosis and diabetes mellitus in a remote period.

To assess intrinsic coagulation pathway factors activity and hemostatic markers of endothelial dysfunction in patients with peripheral artery disease (PAD) before and after lower extremity bypass surgery.80 patients with PAD Fontaine grade IIB-III were enrolled. 40 patients underwent open aorto-femoral-popliteal repair (group A) and 40 patients - medication (group B). Before and in 3 months after surgery peripheral venous blood samples were collected to assess the activity of factors VIII, IX, XI, von Willebrand factor (VWF), protein C (PrC), and metabolites of nitric oxide II (NO).Increased preoperative activity of VIII, IX, XI, and VWF factors compared with normal values was observed in group A. After 3 months there was an additional increase of VIII and VWF factors' activity. Activity of IX and XI factors remained increased on background of reduced level of NO metabolites. In group B increased activity of IX, XI, and VWF factors was revealed while levels of NO metabolites and PrC were normal.Thus, PAD is followed by prothrombotic state especially in patients after surgery. Surgical procedures are associated with more severe hypercoagulation.Цель исследования ― оценить активность факторов внутреннего каскада коагуляции и гемостатических маркеров дисфункции эндотелия у пациентов до и после реконструктивно-восстановительных операций на артериях нижних конечностей. Материал и методы. В исследование были включены 80 пациентов с облитерирующим атеросклерозом артерий нижних конечностей (ОААНК) IIБ―III стадии по Покровскому―Фонтейну. Из них 40 пациентов с ОААНК подверглись открытым вмешательствам на аортобедренно-подколенном сегменте (1-я группа), и 40 пациентов прошли консервативное лечение (2-я группа). При включении больных в исследование и через 3 мес после операции были взяты образцы венозной крови для оценки активности факторов свертывания крови VIII, IX, XI, фактора фон Виллебранда (ФВ), оксида азота II и протеина С (ПрС). Результаты. У пациентов 1-й группы средние значения активности факторов VIII, IX, XI и ФВ были повышены по сравнению с нормой до оперативного вмешательства. Через 3 мес наблюдался еще больший рост активности факторов VIII и ФВ, сохранялся повышенный уровень IX и XI факторов при снижении показателей метаболитов NO. У пациентов 2-й группы были повышены средние значения активности факторов IX, XI и ФВ при нормальном уровне метаболитов NO и ПрС. Вывод. Таким образом, у больных с ОААНК определялось исходное протромбогенное состояние системы гемостаза, более выраженное у оперированных пациентов. Оперативное вмешательство приводит к еще большему сдвигу в сторону гиперкоагуляции.

Effective treatment of chronic lower limb ischemia is one of the most challenging issues confronting vascular surgeons. There are a number of choices available to the vascular surgeon. Open or endovascular revascularization is the treatment of choice when applicable. Current pharmacological therapies play an auxiliary role and cannot prevent disease progression. Therefore, new methods of treatment are needed. We conducted a phase 2b/3 multicenter randomized controlled clinical trial of the intramuscular transfer of a plasmid DNA encoding vascular endothelial growth factor (VEGF) 165 with cytomegalovirus promotor (CMV) in patients with atherosclerotic lower limb ischemia. A total of 100 patients were enrolled in the study, that is, 75 patients were randomized into the test group and received 2 intramuscular injections of 1.2 mg of pCMV- vegf165, 14 days apart together with standard pharmacological treatment. In all, 25 patients were randomized into the control group and received standard treatment only. The following end points were evaluated within the first 6 months of the study and during a 1.5-year additional follow-up period: pain-free walking distance (PWD), ankle–brachial index (ABI), and blood flow velocity (BFV). The pCMV- vegf165 therapy appeared to be significantly more effective than standard treatment. The PWD increased in the test group by 110.4%, 167.2%, and 190.8% at 6 months, 1 year, and 2 years after treatment, respectively. The pCMV- vegf165 intramuscular transfer caused a statistically significant increase in ABI and BFV. There were no positive results in the control group. Thus, pCMV- vegf165 intramuscular gene transfer is an effective method of treatment of moderate to severe claudication due to chronic lower limb ischemia.

Thromboses and stenoses of permanent vascular access appear to be a serious hazard for patients with end-stage kidney disease on programmed haemodialysis. Relapses of these pathological conditions are the cause of repeated hospitalization, secondary surgical interventions and may eventually lead to impossibility of carrying out procedures of haemodialysis. Often, vascular access dysfunction occurs for no apparent reason, thus underlying the importance of studies aimed at revealing additional factors of intravascular thrombogenesis and neointimal formation in a vascular access, including the works dedicated to studying genetic predictors of the development of the above-mentioned complications. The authors examined herein the role of polymorphisms of the genes of endothelin-1 (END-1), nitric oxide synthase-3 (NOS-3), angiotensinogen-2 (AGT-2), angiotensinogen-1 (AGT-1), angiotensinogen 2 receptor type 1 (AGTR1), mitochondrial superoxide dismutase-2 (SOD-2), catalase (CAT) superoxide dismutase-1 (SOD-1) and angiotensin converting enzyme (ACE) in the functional state of permanent vascular access in patients on dialysis. The obtained results demonstrated direct cause-and-effect relationships between polymorphisms lys-198 asn in the END-1 gene, C60T, T58C in the SOD-2 gene and the function of vascular access. The presence of END-1 gene lys-198 asn polymorphism in a homozygous state (allele 1) was associated with a high risk of an unsatisfactory condition of permanent vascular access (p=0.019).Для больных с терминальной стадией хронической почечной недостаточности, находящихся на программном гемодиализе, большую опасность представляют тромбозы и стенозы постоянного сосудистого доступа. Рецидивы данных патологических состояний являются причиной неоднократных госпитализаций, повторных хирургических вмешательств и могут в итоге вести к невозможности дальнейшего проведения процедуры гемодиализа. Нередко дисфункция сосудистого доступа возникает без очевидных причин, что обусловливает актуальность исследований, направленных на выявление дополнительных факторов внутрисосудистого тромбообразования и неоинтимального образования в сосудистом доступе, в том числе работ, посвященных исследованию генетических предикторов развития вышеуказанных осложнений. В работе исследована роль полиморфизма генов эндотелина-1 (END-1), синтазы окиси азота-3 (NOS-3), ангиотензиногена-2 (AGT-2), ангиотензиногена-1 (AGT-1), рецептора 1 типа ангиотензиногена 2 (AGTR1), митохондриальной супероксиддисмутазы-2 (SOD-2), каталазы (CAT), супероксиддисмутазы-1 (SOD-1) и ангиотензин-превращающего фермента (ACE) в функциональном состоянии постоянного сосудистого доступа у пациентов на диализе. Результаты работы показали наличие прямых причинно-следственных связей между полиморфизмами lys-198 asn в гене END-1, C60T, T58C в гене SOD-2 и функцией сосудистого доступа. Наличие полиморфизма lys-198 asn гена END-1 в гомозиготном состоянии (аллель 1) было ассоциировано с высоким риском неудовлетворительного состояния постоянного сосудистого доступа (p=0,019).

The article presents the results of the comparative six-month surveillance inoperable patients with atherosclerosis of lower extremities with clinical manifestations in the form of intermittent claudication (IIa-III century. AVPokrovskii to Fontaine), which are composed of conservative therapy received the drug genterapevtichesky "Neovaskulgen", a plasmid with the gene structure of vascular endothelial growth factor. The study included 50 patients (35 – in the clinical group and 15 – in the control group). The drug was administered intramuscularly, as close as possible to areas of ischemia, twice, at doses of 1.2 mg, with an interval of 14 days. Patients kontralirovlai: the length of pain-free walking distance, ankle-brachial index, transcutaneous oxygen napryazhdenie determined, the linear velocity of blood flow in the affected segment. It is established that in the clinical group were significantly increasing the length of pain-free walking distance, the linear velocity krovtoka. To a lesser extent the other indicators are growing. In the control group had deterioration of patients. The obtained results show the effectiveness of the drug "Neovaskulgen."

Restriction of blood flow due to atherosclerosis leads to chronic lower limb ischemia (CLI) affected 3-8% of the general population. Current pharmacological therapies have limited effects. Therefore, developing new treatments is pivotal. Gene therapy is targeted at inducing angiogenesis in ischemic extremities via increased endogenous expression of vascular growth factors. Among many, plasmid DNA vectors play a significant role in gene therapy and are safe with low immunogenicity and no risk of insertional mutagenesis.A novel drug “Neovasculgen” became the first gene therapy for patients with CLI approved by regulatory authorities in Russia in 2011. It contains a plasmid DNA encoding vascular endothelial growth factor VEGF165 (pCMV-vegf165). There was conducted a multicentre randomised controlled clinical trial of the intramuscular transfer of this new gene product in 100 patients with CLI, stage 2a-3 disease according to Fontaine. The trial lasted 6 months. It was concluded that pCMV-vegf165 transfer significantly improved pain-free walking distance (PWD) and caused no adverse effects. Efficacy and safety of this therapy were evaluated and translated into practice. Most of patients enrolled in the trial gave their consent to participate in the long-term follow-up study. The primary endpoint was PWD, the secondary – ankle-brachial index (ABI) and transcutaneous oxygen tension (TcPO2).PWD in patients who received pCMV-vegf165 increased throughout the 3-year follow-up period: by the end of the 1st year the parameter increased by 167.2% as compared to the 135.3 m baseline (p