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.

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). Methods Materials and 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% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028). Conclusion 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.

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Aim. To study changes in the topography of the orifice of the deep femoral artery (DFA), markers of proliferation, and apoptosis in patients after open interventions on the femoropopliteal arterial segment. Methods. The study included 35 patients with atherosclerotic peripheral arterial disease (PAD), femoral-popliteal occlusion, stage IIBIII of the disease according to the classification of A.V. PokrovskyFontaine, who underwent open surgery. The average age of the patients was 694.6 years. These patients included 26 men. Patients were divided into two groups: group A included 18 patients who underwent femoral-popliteal prosthetics (distal End-To-End bypass anastomoses), group B included 17 patients with femoral-popliteal bypass surgery (distal End-To-Side bypass anastomoses). The groups were comparable in terms of age and disease severity (p 0.05). Determination of serum platelet-derived growth factor BB (PDGF BB) and soluble form Fas (sFas) levels was carried out immediately before the intervention, on the 1st, 7th days, and 1 month after the operation. Duplex scanning (DS) was performed on day 7, after 1 and 18 months. Statistica 10.0 software was used for statistical data processing. The significance of differences between unrelated samples was assessed using the Student's t-test. The correlations between variables were analyzed by using Pearson's method. Results. On 1st day, there was a decrease in soluble Fas in patients of group A compared with group B (0.41 ng/ml vs 0.78 ng/ml, p=0.01). On the 7th day, the levels of serum platelet-derived growth factor BB were increased in patients of group A compared with group B (35.2 ng/ml vs 23.2 ng/ml, p=0.00001). After 1 month, the level of serum platelet-derived growth factor BB in patients of group A remained elevated compared with those in patients of group B (22.8 ng/ml vs 14.4 ng/ml, p=0.0003). Conclusion. Femoropopliteal prosthetics leads to a change in branching angle of the deep femoral artery up to 7080%, accompanied by changing dynamics of apoptotic markers and cell proliferation, leading to an increase in the thickness of neointimal hyperplasia and the progression of atherosclerosis.

Рязанский государственный медицинский университет, г. Рязань, Российская Федерация Апоптоз представляет собой модель генетически запрограммированной гибели клеток и основной механизм, с помощью которого ткань удаляет ненужные или поврежденные клетки. Как в физиологических, так и в патофизиологических условиях различные факторы, включая механические силы, активные формы кислорода и азота, цитокины, окисленные липопротеины, могут влиять на апоптоз сосудистых клеток. Сигнальный путь гибели Fas / Fas-лиганда / каспазы, семейство белков Bcl-2 / митохондрии, ген супрессии опухоли p53 и протоонкоген c-myc могут активироваться в атеросклеротических поражениях и опосредовать гибель клеток во время развития атеросклероза. Аномальная экспрессия и дисфункция этих генов, регулирующих апоптоз, могут ослаблять или ускорять гибель сосудистых клеток и влиять на целостность и стабильность атеросклеротических бляшек. Выяснение молекулярного механизма, который регулирует клеточную гибель, может помочь разработать новую стратегию лечения атеросклероза и таких осложнений, как рестеноз зоны реконструкции. На сегодняшний день до конца остается неясна роль показателей апоптоза в развитии атеросклероза и его основных осложнений. Требуется дальнейшее изучение данной проблемы для более глубокого понимая патогенеза атеросклероза и рестеноза зоны реконструкции и разработки эффективных методов лечения.Ключевые слова: апоптоз, рестеноз, атеросклероз, белки Bcl-2, каспазы Apoptosis is a model of genetically programmed cell death and the main mechanism that allows to remove the unwanted, old or damaged cells. In both physiological and pathophysiological conditions, various factors, including mechanical forces, reactive oxygen and nitrogen forms, cytokines, oxidized lipoproteins can affect vascular cell apoptosis. The signaling pathway of Fas / Fas-ligand / caspase death, the Bcl-2 / mitochondria family of proteins, the p53 tumor suppression gene, and the c-myc protooncogene can be activated in atherosclerotic lesions and mediate cell death during the development of atherosclerosis. Abnormal expression apoptosis-regulating genes and their dysfunction can weaken or accelerate apoptosis of vascular cells and affect the integrity and stability of atherosclerotic plaques. Further findings of the mechanism that regulates apoptosis can help develop a new treatment strategy for atherosclerosis and its main complication, restenosis of the reconstruction zone. At present, the role of apoptosis indicators in the development of atherosclerosis and its main complications remains unclear. Further study of this problem is required for a deeper understanding of atherosclerosis pathogenesis and restenosis of the reconstruction zone and the development of effective treatment methods.