[Adiponectin gene expression in local fat depots in patients with coronary heart disease depending on the degree of coronary lesion].

AIM: To determine the dependence of adiponectin gene expression by subcutaneous, epicardial and perivascular adipocytes on the degree of coronary lesion in coronary heart disease. MATERIALS AND METHODS: 84 patients with coronary artery disease were examined. Of these, 39 people showed a moderate degree of atherosclerotic lesion of the coronary bed (less than or equal to 22 points) on the SYNTAX Score scale, 20 severe (2231 points), and 25 extremely severe (more than 32 points). Upon admission to the hospital, all patients underwent an echocardiographic study (Echocardiography, Acuson, Germany) with the calculation of the ejection fraction (EF) of the left ventricle (LV) to assess its systolic function. During a planned surgical intervention (coronary bypass surgery, CABG), adipocytes of subcutaneous, epicardial (EAT) and perivascular adipose tissue (PVAT) were taken. Adiponectin gene expression was evaluated by polymerase chain reaction (real-time PCR) using TaqMan probes. Statistical analysis was performed using Statistica 9.0. RESULTS: The maximum level of adiponectin expression was detected in adipocytes of PVAT, and the minimum EAT. With an increase in the degree of atherosclerotic lesion of the coronary bed, the expression of the adiponectin gene in adipocytes of local depots significantly decreases r=-0.82; p=0.023. Moreover, the low level of gene expression in EAT correlated with a decrease in LV EF by r=0.73; p=0.03. In adipocytes of subcutaneous and especially PVAT, gene expression was the highest in patients with a moderate degree of coronary lesion. CONCLUSIONS: Low adiponectin gene expression in EAT is associated with an increase in the degree of atherosclerotic lesion of the coronary bed and a decrease in LV EF.

[Ghrelin Physiology and Pathophysiology: Focus on the Cardiovascular System].

Ghrelin is a multifunctional peptide hormone, mainly synthesized by P / D1 cells of the stomach fundus mucosa. Its basic effect, which is realized via GHS-R1 α receptor in the arcuate and the ventromedial nucleuses of hypothalamus, is stimulation of the synthesis of pituitary hormones. Ghrelin is involved in control of appetite and energy balance, regulation of carbohydrate and lipid metabolism, cell proliferation and apoptosis, as well as modulation of functioning of gastrointestinal, cardiovascular, pulmonary and immune systems. It was found that cardiomyocytes are able to synthesize ghrelin. High concentrations of GHS-R1α in the heart and major blood vessels evidence for its possible participation in functioning of cardiovascular system. Ghrelin inhibits apoptosis of cardiomyocytes and endothelial cells, and improves the functioning of the left ventricle (LV) after injury of ischemia-reperfusion mechanism. In rats with heart failure (HF) ghrelin improves LV function and attenuates development of cardiac cachexia. In addition, ghrelin exerts vasodilatory effects in humans, improves cardiac function and reduces peripheral vascular resistance in patients with chronic HF. The review contains of the predictive value of ghrelin in the development and prevention of cardiovascular disease.

Influence of visceral obesity on the secretion of adipokines with epicardial adipocytes in patients with coronary heart disease.

AIM: To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. MATERIALS AND METHODS: Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. RESULTS: It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. CONCLUSION: Thus, the disease on the background of the status of the adipocytes of EAT characterized as a "metabolic inflammation", and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.

Adipokine and Cytokine Profiles of Epicardial and Subcutaneous Adipose Tissue in Patients with Coronary Heart Disease.

The content of adipokines, pro- and anti-inflammatory cytokines were studied in adipocytes isolated from epicardial and subcutaneous adipose tissue of 24 coronary heart disease patients. The content of leptin and soluble leptin receptor in adipocytes of epicardial adipose tissue was higher by 28.6 and 56.9% and the level of adiponectin was lower by 33% than in adipocytes of the subcutaneous fat. In culture of epicardial adipocytes, the levels of proinflammatory cytokines TNF-α and IL-1 were higher. Subcutaneous adipose tissue adipocytes were characterized by higher levels of anti-inflammatory cytokines IL-10 and FGF-ß. In epicardial adipocytes of coronary heart disease patients, the concentrations of leptin, TNF-α, and IL-1 were higher, while the levels of defense regulatory molecules (adiponectin, IL-10, and FGF-ß) were lower than in subcutaneous adipocytes.

[THE ROLE OF LOW-FREQUENCY PIEZOTHROMBOELASTOGRAPHY IN THE COMPREHENSIVE EVALUATION OF HEMOSTASIS IN CORONARY BYPASS SURGERY WITH CARDIOPULMONARY BYPASS].

Aim: To monitor the hemostatic system during platelet concentrate transfusions using low-frequency piezothromboelastography in patients with coronary bypass surgery given aspirin therapy. Materials and Methods: The study involved 148 patients with coronary bypass surgery, with 76 ones undergoing intraoperative transfusion of platelet concentrate and 72 treated without transfusion. The control group consisted of 20 healthy individuals. In the perioperative period indicators of vascular-platelet, coagulation, anticoagulant and fibrinolytic components of hemostasis were evaluated by low-frequency pezotromboelastography using the ARP-01M "Mednord" hardware and software system (Russia). Results: It was shown that the antiplatelet effect of aspirin in the preoperative period was manifest as inhibition of the initial stage of blood coagulation accompanied by increased thrombin potential, the total gain of anticoagulant and fibrinolytic activity of the blood. Heart-lung bypass was accompanied by structural and chronometric anticoagulation, reduction of anticoagulation and increase of blood fibrinolytic activity. In the postoperative period, structural and chronometric anticoagulation was more pronounced in patients who did not undergo transfusion of platelet concentrate than in the group of patients with transfusion. Donor platelets further increased the blood hemostatic potential by neutralizing the antiplatelet effect of aspirin. Perioperative thrombohemorrhagic complications were absent in both groups. Conclusion: Low-frequency piezothromboelastography provides a tool for real-time monitoring the functional state of hemostasis system. Transfusion of platelet concentrate is not advisable given that the thrombin potential is preserved as confirmed by the results of low-frequency piezothromboelastography.

[The physiologic and pathophysiologic role of stimulating growth factor ST2.]

The ST2 is a member of family of receptors of interleukin I (IL-I) and consists of two isoforms: a trans-membrane of cellular one (ST2L) and soluble or circulating one (sST2). The ST2 is a receptor of IL-33 that represents IL-I like cytokine. The IL-33 manifests its cellular functions binding receptor complex consisted of accessory protein ST2L and IL-IR. The system IL-33/ST2 is activated in cardiomyocytes and fibroblasts in response to mechanical irritation or damage. It was demonstrated that interaction between IL-33 and ST2L is a cardioprotective one. The experimental models were used to demonstrate decreasing of myocardium fibrosis, prevention of development of hypertrophy of cardiomyocytes, decreasing of apoptosis and amelioration of functional capacity of myocardium at interaction of IL-33 and ST2L. In particular, the positive effects of IL-33 are related to receptor of ST2L. In turn, sST2 by binding with IL-33 sets blocking of interaction between IL-33/ST2L hence eliminating cardioprotective effects. During last years, the knowledge about the role of ST2 in pathophysiology of cardio-vascular diseases broadened and now the role of ST2 is related to myocardium dysfunction, fibrosis and remodeling. The system IL-33/ST2L, besides its myocardial role, can play an additional role in development and progressing of atherosclerosis. The system IL-33/ST2L can have a therapeutic potential in case of myocardial overload or trauma. On the contrary, sST2 acts as a false receptor of IL-33 blocking cardioprotective effects of interaction of IL-33/ST2L.

[The advantage of test on thrombin generation for evaluation of hemostasis potential under implementation of coronary bypass surgery in patients with ischemic heart disease.]

The purpose of study is to evaluate peri-operational parameters of testing of generation of thrombin and its relationship with indices of coagulation hemostasis, fibrinolytic system and anti-coagulants in patients with ischemic heart disease under coronary bypass surgery in conditions of artificial blood circulation. The examined sampling included 200 patients with ischemic heart disease. The planned primary operation of coronary bypass surgery in conditions of artificial blood circulation was applied to all of them. The testing of generation of thrombin was implemented using automated analyzer CEVERON-ALPHA (Technoclone, Vienna, Austria). The indices of testing of generation of thrombin were compared with common techniques of evaluation of hemostasis (INR, PTT, fibrinogen, Qick's prothrombin testing, thrombin time, AT-III, protein C, factor VIII), von Willebrand factor, inhibitor of activation of plasminogen type I (PAI-I), tissue and urokinase plasminogen activator. It is demonstrated that application of testing of thrombin generation duplicates enumerated indices and permits at the same time instant to detect both pro-coagulation and anti-thrombotic shifts. The advantage of testing of thrombin generation is in evaluation of thrombin potential that is most actual in cardiologic practice.

[Diagnostic value of the stimulating growth factor ST2 during hospitalization for myocardial infarction]. / Diagnosticheskoe znachenie stimuliruyushchego faktora rosta ST2 v gospital'nom periode infarkta miokarda.

AIM: To determine the concentration of the stimulating growth factor ST2 and its relationship to the clinical course of myocardial infarction (MI) over time during hospitalization. MATERIALS AND METHODS: Eighty-eight MI patients whose mean age was 59±8.36 years were examined. On days 1 and 12 of MI, the serum levels of ST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were determined by ELISA. A control group consisted of 30 people. RESULTS: On day 1 of hospitalization for MI, the concentrations of ST2 and NT-proBNP were higher 2.4 and 4.5 times, respectively, than those in the controls; by day 12, there was a statistically significant decrease in the level of ST2 while that of NT-proBNP was unchanged. During hospitalization, the investigators recorded MI complications, according to which the patients were divided into favorable and unfavorable MI groups. On day 1 of hospitalization, the level of ST2 in the patients with unfavorable MI was twice higher than in those with favorable MI and 3.7 times higher than in the control group. On day 12, both favorable and unfavorable MI groups showed a reduction in the level of the marker. On day 1 of MI, the concentration of NT-proBNP in the patients with a poor prognosis was 6.8 times greater than in the controls and 1.8 times more than in the patients with a good prognosis. On day 12, NT-proBNP levels remained elevated in both groups. Logistic regression analysis revealed that the determination of ST2 in combination with NT-proBNP increased their diagnostic significance (odds ratio, 1.92; 95% CI, 1.7-3.2; area under characteristic curve, 0.89; p=0.004). CONCLUSION: The level of ST2 was a more sensitive indicator of hospitalization for MI than that of NT-proBNP. The combined use of ST2 and NT-proBNP was found to have a high diagnostic sensitivity and specificity.

[Evaluation of the hemostatic potential at coronary artery bypass surgery during long-term aspirin therapy]. / Otsenka gemostaticheskogo potentsiala krovi pri operatsiyakh koronarnogo shuntirovaniya na fone dlitel'noi terapii atsetilsalitsilovoi kislotoi.

AIM: To estimate thrombin generation test parameters in patients with coronary heart disease during coronary artery bypass surgery under extracorporeal circulation after transfusion of donor platelet concentrates during long-term therapy with acetylsalicylic acid (ASA). SUBJECTS AND METHODS: A total of 148 patients with coronary heart disease who had undergone elective primary coronary artery bypass surgery under extracorporeal circulation during preserved therapy with ASA (75-100 mg/day) were examined. According to donor platelet concentrate transfusion, all the patients were divided into 2 groups: 1) 76 patients undergoing donor platelet transfusion and 2) 72 without this procedure. A control group consisted of 20 apparently healthy individuals. At the pre-, intra-, and early postoperative stages, the investigators evaluated the following thrombin generation test parameters: lag time (min); peak thrombin concentration (nM/l); time to peak (min); the area under the thrombin generation curve (nM), and thrombin generation rate (nM/min). RESULTS: During long-term ASA therapy, the patients were found to have an activated endogenous thrombin potential in the pre- and intraoperative periods, as evidenced by the high peak concentration of thrombin and the increased rate of its generation. At the same time, the time of prothrombinase complex activation and that of thrombin generation were longer than those in the control group. In the early postoperative period, the patients who had not been transfused with platelet concentrates with a further increase in the temporal parameters, showed a decreased hemostatic potential, reaching the control level, whereas donor platelet transfusion stimulated endogenous thrombin generation: the time to initiate clotting and that to reach the peak were shorter; in this case, the thrombin generation rate and concentrations increased, but the preoperative level was not reached. No perioperative (hemorrhagic or thrombotic ischemic) events were noted in the examined groups. CONCLUSION: The hemostatic potential was preserved in patients receiving long-term therapy for ASA. Taking into account laboratory and clinical findings, platelet concentrate transfusions are unnecessary for preventive purposes. The appropriateness of donor platelet transfusion should be strictly individually approached with regard to the laboratory parameters of the thrombin generation test, by minimizing the risk of perioperative ischemic and hemorrhagic events in each specific patient.

[The possibility of application of stimulant growth factor (ST2) for verifying postinfarction remodeling of myocardium.]

PURPOSE OF STUDY: To detect level ST2 in blood serum of patients with myocardium infarction in dynamics of hospital period and their relationship with remodeling of myocardium. MATERIALS AND METHODS: The study sampling included 87 patients (65 males and 22 females) with myocardium infarction and the ST-segment elevation and average age of 59 years. All patients were allocated in two groups: with adaptive alternative of remodeling of myocardium (67 patients) and deadaptive alternative (20 patients). The control group consisted of 30 individuals. At the first and twelfth days after myocardium infarction in blood serum content of ST2 and NT-proBNP were detected using immune-enzyme technique with application of test-systems produced by Critical Diagnostics (USA) and Biomedica (Slovakia) correspondingly. The data statistical analysis was processed using non-parametric criteria. THE RESULTS: He content of ST2 and NT-proBNP at the first day of myocardium infarction increased in 2.4 and 4.5 times correspondingly as compared with control group. The patients with deadaptive remodeling were characterized by in 1.5 times higher content of ST2 at the first day than in group of adaptive remodeling and in 5.3 times higher that in control group. In the end of hospital period (twelfth day) in both groups decreasing of level of ST2 was observed. The concentration of NT-proBNP at the first day was increased in 1.8 times in patients of both groups and decreased at twelfth day. At that there were no differences between both groups. The high level of ST2 at the first day increases the risk of development of deadaptive remodeling in 4.5 times, NT-proBNP only in 2.3 times. CONCLUSION: The high level of stimulant growth factor ST2 at the first day of myocardium infarction was associated with deadaptive alternative of post-infarction remodeling that permits using ST2 as prognostic marker with high sensitivity and specificity.

[IMMUNOGENETICS AND PROGRESSION OF CHRONIC VIRAL HEPATITES].

AIM OF INVESTIGATION: To estimate the role of polymorphic variants of genes IL4 (C-590T), IL4RA (I50V), TNF (G-308A) and SLC1IAI (D543N) in chronic viral hepatitis progression. MATERIAL AND METHODS: Overall 121 patients with chronic viral hepatitis C and B. RESULTS: Study results have demonstrated, that of all investigated polymorphic variants of genes IL4 (C-590T), IL4RA (150V), TNF (G-308A) and SLC11A1 (D543N) in patients with chronic liver diseases of various etiology the <> IL4RA gene variant (II50Val) is associated with HBV-infection chronization. The allele <> gene TNF-α (G-308A) is protective for chronic viral hepatitis and is associated with a low level of production by mononuclear cells of TNF-α and IL-12, high secretion of IL-4 and low degree of collagenopathy in the liver. Genotype <> of IL4 (C-590T) gene is an adverse marker for progression of chronic viral hepatitis B. There was significant correlation of polymorphic variants TNF (G-308A) and IL4 (C-590T) genes with production of the key interleukins, that determine type of immune response (Th-1, Th-2) and products of collagen metabolism that testifies genetic determination of system immune response and collagen formation processes in the liver at chronic viral hepatitis.

[Biochemical characteristics associated with diabetes mellitus one year after myocardial infarction].

AIM: To evaluate the most informative parameters of adipokine, anti-inflammatory, and prothrombogenic status associated with diabetes mellitus. MATERIALS AND METHODS: The study included 200 patients with myocardial infarction (MI) in whom markers of adipokine status, grelin, anti-inflammatory factors, CRP and plasminogen activator inhibitor were measured by biochemical methods on days 1 and 12 after admission. RESULTS: In the period of acute MI, the adipokine status was disturbed, FFA and grelin levels decreased, pro-inflammatory and thrombotic potential increased. Patients who developed diabetes within 1 year after MI were characterized by more pronounced changes of the parameters of interest. CONCLUSION: Adiponectin, retinol-binding protein, grelin, TNF-α, and plasminogen activator inhibitor are the most informative biochemical parameters associated with diabetes mellitus developing 1 year after MI.

[The markers of lipid transport system of blood and annual prognosis of cardiac infarction].

The sampling included 133 patients with diagnosis of cardiac infarction with peak of segment ST. After a year after old cardiac infarction, in 38 patients were established such unfavorable outcomes of disease as progressive stenocardia, decompensation of cardiac failure, repeated cardiac infarction and lethal outcome. It is established that among all indicators of lipid profile detected at hospital period of cardiac infarction only three indicators are prognostically significant in groups of patients with different outcomes--levels of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them. During hospital period, augmentation of concentration of free fatty acids, oxidized modified lipoproteins of low density and antibodies to them increases risk of development of distant complications of cardiac infarction. The mathematical model is proposed comprising as predictors free fatty acids and antibodies to oxidized modified lipoproteins of low density. This model makes it possible on the basis of biochemical data obtained during hospital period, to calculate individual cumulative risk and to develop long-term prognosis of probable outcome of cardiac infarction.

[Lipid, adipokine and ghrelin concentrations in myocardial infarction patients with insulin resistance].

AIM: The estimate insulin resistance in myocardial infarction. PATIENTS AND METHODS: The study involved 200 patients with myocardial infarction, in which on the 1st and 12th day of hospitalization measured glucose, insulin, insulin resistance index (IR), lipid profile, the concentration of adipokines and ghrelin. RESULTS: IR was detected in 77% of patients and was associated with a history of factors of cardiovascular risk, adverse clinical course of the disease, lipid disorders. The most important marker was the level of free fatty acids. High risk associated with increased in 9 times the concentration of free fatty acids in blood plasma. Patients with IR observed increased concentrations of leptin, resistin, and reduced the protective effect of adiponectin. The high specificity and sensitivity characteristic of the concentration of ghrelin: its reduction by 4 times in the acute phase of myocardial infarction increases the risk of MI by 78%. CONCLUSIONS: Significant risk factors for MI myocardial infarction, along with insulinemia and glycemia, is to increase the concentration of free fatty acids and the disbalance in the system adipokines against deficiency of ghrelin in acute and early recovery periods of the disease. Free fatty acids and ghrelin are promising markers to stratify the risk of insulin myocardial infarction. resistance in patients with myocardial infarction.

[The detection of leptin and metabolic markers of insulin resistance in patients with myocardial infarction].

The shortage of data concerning the character of changes of leptin concentration and its role information of insulin resistance under development of acute coronary events determined the appropriateness of the present study. The cardiac infarction patients with and without diabetes type II were examined. The identified hyperleptinemia, its relationship with basal and post-prandial hyperglycemia and with increase of C-peptide concentration and free fatty acids made possible to consider leptin both as one of the important components in the series of carbohydrate and lipid metabolism disorders and the additional marker of development of insulin resistance under cardiac infarction. These study results can be applied to patients with diabetes anamnesis and to patients without this concomitant pathology. The study results can be used as a foundation for new diagnostic and therapy tactics of metabolic disorders correction in patients with acute coronary vascular pathology.

Alpha-2 macroglobulin activity in SARS-CoV-2 induced infection and in the post-COVID-19 period.

The universal proteinase inhibitor α2-macroglobulin (α2-MG) exhibiting antiviral and immunomodulatory activities, is considered as an important participant in the infectious process. The activity of α2-MG in the new coronavirus infection and post-covid syndrome (long COVID) has not been studied yet. We examined 85 patients diagnosed with community-acquired bilateral polysegmental pneumonia developed under conditions of a new coronavirus infection SARS-CoV-2. For assessment of the post-COVID period, 60 patients were examined 5.0±3.6 months after the coronavirus infection. Among these patients, 40 people had complications, manifested in the form of neurological, cardiological, gastroenterological, dermatological, bronchopulmonary symptoms. The control group included 30 conditionally healthy individuals with a negative PCR result for SARS-CoV-2 RNA and lack of antibodies to the SARS-CoV-2 virus. The α2-MG activity in serum samples of patients with coronavirus infection dramatically decreased, up to 2.5% of the physiological level. This was accompanied by an increase in the activity of the α1-proteinase inhibitor, elastase- and trypsin-like proteinases by 2.0-, 4.4- and 2.6-fold respectively as compared with these parameters in conditionally healthy individuals of the control. In the post-COVID period, despite the trend towards normalization of the activity of inhibitors, the activity of elastase-like and especially trypsin-like proteinases in serum remained elevated. In overweight individuals, the increase in the activity of trypsin-like proteinases was most pronounced and correlated with an increase in the antibody titer to the SARS-CoV-2 virus. In the post-COVID period, the α2-MG activity not only normalized, but also exceeded the control level, especially in patients with dermatological and neurological symptoms. In patients with neurological symptoms or with dermatological symptoms, the α2-MG activity was 1.3 times and 2.1 times higher than in asymptomatic persons. Low α2-MG activity in the post-COVID period persisted in overweight individuals. The results obtained can be used to monitor the course of the post-COVID period and identify risk groups for complications.

[Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection]. / Proteoliz i defitsit α1-proteinaznogo ingibitora pri infektsii SARS-CoV-2.

The SARS-CoV-2 pandemia had stimulated the numerous publications emergence on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), primarily when it was found that high mortality in some regions corresponded to the regions with deficient α1-PI alleles. By analogy with the last century's data, when the root cause of the α1-antitrypsin, genetic deficiency leading to the elastase activation in pulmonary emphysema, was proven. It is evident that proteolysis hyperactivation in COVID-19 may be associated with α1-PI impaired functions. The purpose of this review is to systematize scientific data, critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a target in therapy. This review describes the proteinase-dependent stages of a viral infection: the reception and virus penetration into the cell, the plasma aldosterone-angiotensin-renin, kinins, blood clotting systems imbalance. The ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases role in the virus tropism, proteolytic cascades activation in blood, and the COVID-19-dependent complications is presented. The analysis of scientific reports on the α1-PI implementation in the SARS-CoV-2-induced inflammation, the links with the infection severity, and comorbidities were carried out. Particular attention is paid to the acquired α1-PI deficiency in assessing the patients with the proteolysis overactivation and chronic non-inflammatory diseases that are accompanied by the risk factors for the comorbidities progression, and the long-term consequences of COVID-19 initiation. Analyzed data on the search and proteases inhibitory drugs usage in the bronchopulmonary cardiovascular pathologies therapy are essential. It becomes evident the antiviral, anti-inflammatory, anticoagulant, anti-apoptotic effect of α1-PI. The prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders are presented.

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.

The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α1-PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α1-antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α1-PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone-angiotensin-renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α1-PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α1-PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α1-PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.

[The detection of oxidation-modified lipoproteins and their antibodies in case of complicated course of myocardial infarction with segment ST boost].

According contemporary conceptions, the key role in the development of atherosclerosis play the low density oxidative modified lipoproteins and its antibodies. The purpose of the study was to discover the characteristics of changes in lipid metabolism indicators, including the low density oxidative modified lipoproteins and their antibodies. The factors of oxidative status in patients with cardiac infarction with complicated and non-complicated course were considered. It is established that the development of cardiac infarction is followed the increase of concentration of low density oxidative modified lipoproteins and their antibodies both during the first day after acute pain syndrome and stabilization period. The evaluation of content of low density oxidative modified lipoproteins and their antibodies broaden the possibilities of diagnostics, prognosis and decrease of risk of development both acute and recurrent coronary events.

[The parameters of collagen proteolytic and metabolic systems in chronic liver diseases of viral and toxic etiologies].

AIM: To study a relationship of the plasma activity of elastase-like and collagenase-like proteinases and their inhibitors to hepatic collagen metabolism and to detect the serum markers of fibrosis severity. SUBJECTS AND METHODS: Three hundred and fifty-nine patients with chronic liver diseases (CLD), including 118 patients with chronic viral hepatitis (CVH), 113 with CVH concurrent with alcoholic liver disease (ALD), 109 with ALD, and 19 with CLD in the presence of opiomania were examined. The activities of alpha1-proteinase inhibitor and alpha2-macroglobulin (alpha2-MG) were determined by the unified spectrophometric assay from the inhibition of N-benzoyl-arginine ethyl ester hydrolysis. The activity of elastase-like proteinases was determined by enzymatic assay from the hydrolysis of the synthetic substrate N-butyloxycarbonyl-L-alanine-para-nitrophenyl ester. That of collagenase-like proteinases was determined, by using a collagen type 1 substrate and expressed in terms of micromoles of the resultant hydroxyproline. The content of hydroxyproline was determined by a color reaction with demethylbenzaldehyde, a free, peptide- and protein-bound hydroxyproline; their fraction was obtained under various conditions of plasma protein isolation and hydrolysis. Plasma fibronectin levels were measured by solid-phase immunoassay. Liver biopsy specimens were morphologically studied in the majority of patients to determine the histological hepatitis activity index and the stage of fibrosis. RESULTS: Fibrois formation in the liver in its chronic diseases was attended by a significant reduction in the activity of collagenase-like proteinases hydrolyzing collagen and by the lower activity of alpha2-MG, an inhibitor limiting collagen formation. CONCLUSION: The identified changes make themselves evident just in early fibrosis, which suggests the rapid onset of imbalance in the mechanisms responsible for regulation of connective tissue synthesis and promotes intensified fibrosis formation.