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.

Apoptosis is recognized as a programmed cell death controlled by genetic mechanisms and required for normal existence of an organism. Its main task is elimination of defective or mutant cells. The particles of dead cells are engulfed by macrophages with no development of inflammatory reaction. Apoptosis actively participates in embryogenesis, cellular homeostasis, elimination of tumor cells, and may be divided to three phases: signal, effector, and degradation. Its main components are cytoplasmic proteases caspases. Caspases exist in the cytoplasm in inactive condition in the form pf procaspases. Being activated, they break down to subunits. Proteins of Bcl-2 family are active participants of the mitochondrial pathway of apoptosis. They influence permeability of the outer membrane of mitochondria. Disorders in the mechanisms of apoptosis underlie many diseases including ischemic lesions, autoimmune disorders, malignant neoplasms. The ability to influence survival or death of cell is known to possess enormous therapeutic potential. At present, active research is under way to study signal pathways that control cell cycle and apoptosis. The article discusses the mechanisms participating in death of vascular endothelium and smooth muscle cells, potential role of apoptosis in atherosclerosis is also described.

INTRODUCTION: The development and progression of atherosclerosis in different vascular pools remain unclear. Many studies have considered apoptosis to play a key role in the development of atherosclerosis; apoptosis is a programmed cell death with characteristic morphological signs aimed at providing homeostasis in an organism in general and in the vascular wall in particular. However, all studies that have been devoted to markers of apoptosis were mostly experimental and were conducted on either animals or grown cultures of different cells. The study aimed to examine markers of apoptosis (р53, sFas, Вах, and Всl-2) and proliferation (platelet-derived growth factor [PDGF] BB) in the vessel wall in the area of an atherosclerotic lesion in a patient with multifocal atherosclerosis. The clinical case was of interest because it allowed the assessment of biomarkers in both the area of progression of atherosclerotic lesion on an operated limb and the carotid pool in the long-term postoperative period. CONCLUSIONS: This case demonstrated that a patient with obliterating atherosclerosis of the lower limb arteries had an elevated level of pro-apoptotic markers р53 and Вах and PDGF ВВ as a marker of cell proliferation and migration, against the background reduced level of anti-apoptotic markers Всl-2 and sFas in comparison with their values in the normal arterial wall. The progression of atherosclerotic lesion in two vascular pools was associated with a further increase in the values of proapoptotic markers (р53 and Вах) and decrease in the values of Всl-2 and sFas compared with the initial samples. With this, the values of PDGF ВВ marker remained elevated relative to the initial level.

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 3rd 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% CO2. 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 (р0.001), control and PTFE group (р=0.037), Dacron and PTFE (р0.001). Incubation with Dacron led to suppression of metabolic activity of cells by 41.7% as compared to the control group (р0.001). Metabolic activity of cells exposed to PTFE, approached that of the control group, that is, it corresponded to the optimal conditions of culturing of endothelial cells in vitro. Conclusion. In comparison with polyethylene-terephthalate (Dacron), polytetrafluoro-ethylene (PTFE) showed the least suppression of metabolic activity of endothelial cells in vitro.

Introduction: As with many other surgical interventions, the implantation of a pacemaker may be associated with adverse outcomes in the immediate or distant period. The search for probable risk factors of adverse outcomes may promote the development of effective and safe management methods of patients with pacemaker postoperatively. One of the important directions in this field is the investigation of the effect of pacemaker implantation on the hemostasis system of these patients. Aim: To evaluate the effect of the implantation of dual-chamber pacemaker on the hemostasis system of patients with different kinds of bradyarrhythmias and to determine probable risk factors for unfavorable outcomes in this groupof patients. Materials and methods: The study was performed with the financial support of the Russian Foundation for Basic Research within the Scientific Project No. 19-315-90109. The prospective study (ClinicalTrials.gov ID, NCT04499612) enrolled 61 patients (men, 45.9%) with a mean age of 71.5 8.8 years. The groupwho received surgical treatment included 23 patients with atrioventricular (AV) block and 25 patients with sick sinus syndrome (SSS), and the groupwith conservative treatment included 13 patients with AV blocks and SSS, but without indications for pacemaker implantation. Anticoagulant therapy was given to one patient with AV block, 12 patients with SSS, and five patients with conservative therapy. All the remaining patients received antiplatelet therapy. The surgical groupunderwent ultrasound examination of the veins of the upper and lower extremities and sampling of peripheral venous blood before and 7 days after pacemaker implantation to determine the level of fibrinogen (FI) and activity of blood coagulation factors VIII (FVIII) and IX (FIX), antithrombin III (AT III), and protein C. In the conservative group, a similar examination was conducted only on inclusion in the study. Results: In patients with AV block, a significant increase in blood fibrinogen was noted at 7 days after surgery (р=0.042). In the intergroupcomparison, the activity of AT III after the implantation was higher in the surgical groupthan in the conservative group(р=0.018 and р=0.006, respectively). After surgery, the activity of FVIII and FIX was lower in patients with SSS on anticoagulant therapy than in patients with antiplatelet therapy (р=0.048 and р=0.015, respectively). Based on the receiver operating characteristics analysis, the risk factors for lethal outcomes were reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS. Conclusions: The balance of the hemostasis system in patients with AV blocks on antiplatelet therapy was shifted toward hypercoagulation within at least 7 days after pacemaker implantation. The use of anticoagulants in patients with SSS caused a shift toward hypocoagulation. The reduced activity of AT III in patients with AV block and increased activity of FIX in patients with SSS are prognostic factors for lethal outcomes.