Sars-Cov2 Induced Biochemical Mechanisms in Liver Damage and Intestinal Lesions.

Multiple pathogenic mechanisms are found in SARS-CoV2 systemic inflammation. Oxidative stress, altered proteolysis, hypercoagulation, and metabolic disorders are significant in virus-induced lesions. The study aimed to investigate the biochemical mechanism of virus-induced disorders and determine the biochemical features in SARS-CoV2-associated liver damage and intestine lesions. A retrospective case series of ninety-two patients diagnosed with COVID-19 pnemonia. The ACE, α1-proteinase inhibitor, trypsin-like proteinase, and elastase activity were measured. Nitrites level was detected in reaction with Griess reagent. The ELISA kit measured Troponin, C-peptide, leptin, adiponectin, PAR4, and neuropilin level. It was obtained an increase in ACE activity and nitrites ions content in SARS-CoV2 associated patients. The hyperglycemia and an increase in adipose tissue-derived hormones guided the virus-induced metabolic disorders. Proteolysis activation was revealed in SARS-CoV2 pneumonia patients. The found molecular event was accompanied by hyperglycemia induction. Multiorgan lesions manifest in in cardiac failure, which was detected in patients with ARDS. Moreover, high arterial blood pressure in patients with COVID-19 was associated with the hyperglycemia and increased ACE activity and NO ions level. Liver damage was specific for COVID-19-associated patients with severe ARDS and heart failure. Proteolysis overactivation resulting in vasoactive substances imbalance was detected in patients with the intestinal lesions. The obtained data shows the the neuropilin-dependent axis in damage prevalence in the intestine. Metabolic disorders resulting in the growth of adipose-derived tissue hormones, nitrites, and neuropilin levels was triggered by prolonged inflammation. So, the impaired metabolism and SARS-CoV2 associated hyperglycemia influence on SARS-CoV2 multiple mechanisms. Gastrointestinal manifestations in SARS-CoV2 infection was found to be related to various biochemical and molecular tools. ACE2 receptors axis is prevalent for liver damage, but NRP-1 protein (neuropilin), NO derivatives, and adipose tissue-derived hormones are essential for intestinal lesions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01089-x.

Adipocytes Directly Affect Coronary Artery Disease Pathogenesis via Induction of Adipokine and Cytokine Imbalances.

This study aimed to investigate the adipokine and cytokine profiles of adipocytes from epicardial and subcutaneous adipose tissues in interconnection with the visceral adipose tissue area and the biochemical and clinical characteristics of patients with coronary artery disease. We assessed 84 patients with coronary artery disease (65 men, 19 women) and divided them into two groups based on the presence of visceral obesity. We sampled epicardial and subcutaneous adipose tissues from the patients with visceral obesity. We then cultured the adipocytes and evaluated their adipokine profiles and pro-inflammatory activity. Results show that the mRNA expression of adiponectin in cultures of epicardial adipocytes from patients with and without visceral obesity was lower than that in subcutaneous adipocytes. Moreover, adiponectin mRNA expression in cultures of subcutaneous and epicardial adipocytes from patients with visceral obesity was lower than that in patients without obesity. For leptin, the reverse pattern was observed, with expression higher in cultures of epicardial adipocytes than in subcutaneous adipocytes and higher in epicardial adipocytes from patients with visceral obesity than in those from subjects without visceral obesity. In addition, in epicardial adipocytes, increased expression of proinflammatory cytokine genes (IL6, TNF) was observed compared with that in subcutaneous adipocytes. In contrast, expression of IL10 was higher in cultures of subcutaneous adipocytes than in epicardial adipocytes. The epicardial adipose tissue area was associated with the presence of higher levels of leptin and TNF-α within adipocytes and serum, increased lipid and carbohydrate metabolism. Coronary artery disease, in the context of the status of epicardial adipocytes, can be characterized as "metabolic inflammation," suggesting the direct involvement of adipocytes in pathogenesis through the development of adipokine imbalances and activation of proinflammatory processes.

Biological markers and cardiac remodelling following the myocardial infarction.

AIM: To assess growth stimulating factor ST2 and N-terminal pro b-type natriuretic peptide (NT-proBNP) levels in the sera of myocardial infraction (MI) patients, and their correlation with the adaptive and maladaptive variants of cardiac remodelling. METHODS: 87 patients (65 male, 22 females; 67±8.36 years) with ST-elevated MI were included in this study, and 67 patients had an adaptive, physiological, while 20 patients had a maladaptive, pathological variant of myocardium remodelling. RESULTS: On day 1, ST2 and NT-proBNP levels were shown to increase 2.4 and 4.5 folds, respectively, compared with those in the control. ST2 levels in patients with maladaptive remodelling were 1.5-fold higher than those in the adaptive remodelling group. On day 12, a decrease in ST2 levels was observed in both groups. NT-proBNP levels increased 1.8 folds in both groups on day 1, compared with those in the controls. Increased ST2 levels on day 1 after MI were shown to increase the risk of maladaptive remodelling 4.5 folds, while high NT-proBNP levels increased this risk 2.3 times. CONCLUSIONS: ST2 level determination allows us to predict the risk of maladaptive remodelling with a higher sensitivity and specificity than using NT-proBNP levels.

Relationship between epicardial and perivascular fatty tissue and adipokine-cytokine level in coronary artery disease patients.

The aim of this study was to determine the relationship between the thickness of epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) and the adipokine-cytokine profile of patients with coronary heart disease, which can be of significant importance for predicting the course of cardiovascular disease (CVD). Eighty-four patients with CVD were assessed and divided into two groups based on the presence of visceral obesity (VO). In patients with VO, the thickness of the epicardial deposits of the left and right ventricles were 1.75 and 1.43 times greater, respectively, than in patients without VO. For patients with VO, the prevalence of the volume of the left anterior descending artery was 10% higher, and the middle third of the envelope artery was 28% higher, when compared to patients without VO. When evaluating inflammatory status, it was established that the concentration of tumor necrosis factor-α, interleukin (IL)-1ß, and leptin in the blood serum of patients with VO exceeded the values of patients without VO. The level of anti-inflammatory IL-10 was 2-times lower in patients with VO. The findings of this study show that increased EAT and PVAT are independent risk factors of CVD, as well as a possible model for the assessment of drug effectiveness for CVD.

Relationships between epicardial adipose tissue thickness and adipo-fibrokine indicator profiles post-myocardial infarction.

BACKGROUND: Determination of the impact of visceral obesity and epicardial adipose tissue thickness on stimulating growth factor levels during hospitalization for myocardial infarction is of potential importance for predicting outcomes and assessing the development of cardiofibrotic changes associated with maladaptive myocardial remodeling. In this study, we aimed to investigate the relationships between epicardial adipose tissue thickness, adipokine profiles, and the stimulating growth factor 2/interleukin-33 signaling system during hospitalization for myocardial infarction, and with the cardiac fibrosis extent 1-year post-MI in patients with visceral obesity. METHODS: Eighty-eight patients with myocardial infarction were grouped based on their visceral obesity. Serum leptin, adiponectin, stimulating growth factor 2, and interleukin-33 levels were measured on days 1 and 12 and at 1 year. The epicardial adipose tissue widths and the cardiac fibrosis areas were measured on day 12 and at 1 year. RESULTS: Visceral obesity was associated with epicardial adipose tissue thickness increases, adipokine imbalances, elevated leptin levels, and lower adiponectin levels during early hospitalization, and cardiac fibrosis development. Patients without visceral obesity had higher interleukin-33 and stimulating growth factor 2 levels during early hospitalization and lower cardiac fibrosis rates. Epicardial adipose tissue thickness was positively associated with cardiac fibrosis prevalence and interleukin-33 levels and negatively associated with stimulating growth factor 2 levels. The cardiac fibrosis extent was negatively associated with interleukin-33 levels and positively associated with stimulating growth factor 2 levels. CONCLUSIONS: Increases in epicardial adipose tissue thickness are associated with cardiac fibrosis development 1-year post-myocardial infarction and are higher in patients with visceral obesity. The metabolic activity of the epicardial adipose tissue is associated with elevated interleukin-33 and reduced stimulating growth factor 2 levels.

Effect of different doses of statins on the development of type 2 diabetes mellitus in patients with myocardial infarction.

BACKGROUND: Cardiovascular diseases and type 2 diabetes mellitus (T2DM) may have common developmental mechanisms associated with lipid metabolism disorders. Dyslipidemia and progression of atherosclerosis in people with T2DM are accompanied by an increase in cardiovascular mortality. This study examined the dose-dependent action of atorvastatin on carbohydrate metabolism and adipokine status in patients within 12 months after myocardial infarction (MI). METHODS: A total of 156 male MI patients who had received atorvastatin 20 mg/day (78 patients) or 40 mg/day (78 patients) starting from day 1 of onset were enrolled. Glucose, insulin, C-peptide, resistin, adiponectin, and ghrelin levels were measured at baseline, day 12, and months 3 and 12. Patients were monitored for new incidences of T2DM for 12 months after MI. RESULTS: For acute phase MI, patients had moderate insulin resistance, hyperglycemia, and hyper-insulinemia, high leptin and resistin levels, and low ghrelin and adiponectin levels. Atorvastatin 20 mg/day was more effective at correcting the imbalances. Patients taking atorvastatin 40 mg/day (group 2) following MI showed increases in levels of glucose, insulin, and C-peptide and insulin resistance progression after 12 months of therapy, as evidenced by increased quantitative insulin sensitivity check index scores and detection of new T2DM cases. CONCLUSION: Atorvastatin improved adipokine profiles and ghrelin levels, with low doses showing more significant effects. Atorvastatin dose prescribed for MI patients should take into account the degree of insulin resistance and adipokine status.

Use of thrombin generation test for monitoring hemostasis in coronary bypass surgery.

To evaluate the parameters of the thrombin generation test (TGT) in coronary artery disease (CAD) patients on prolonged aspirin therapy during on-pump coronary artery bypass grafting (CABG) after donor platelet concentrate transfusion. A total of 148 patients with CAD on prolonged aspirin therapy (75-100 mg/day) who have undergone elective on-pump CABG were consecutively included in the study. Patients were divided randomly into two groups. Group 1 (n = 76) received donor platelet transfusions after cardiopulmonary bypass, whereas Group 2 (n = 72) did not. TGT parameters were measured using an analyzer at pre-, intra-, and early postoperative periods. Activation of the endogenous thrombin potential was observed in patients on prolonged aspirin therapy in the pre- and intraoperative periods, as confirmed by high peak thrombin and increased velocity index. The activation time of the prothrombinase complex and thrombin generation time were greater than the control group. The blood hemostatic potential in patients who did not receive transfusions in the early postoperative period decreased up to the level of the control group in the extended time parameters. Hemostatic potential in plasma in patients on aspirin was preserved. Given the laboratory test results and clinical data, platelet concentrate transfusion is unnecessary for prevention.

Relationship key factor of inflammation and the development of complications in the late period of myocardial infarction in patients with visceral obesity.

BACKGROUND: Cytokines play an significant role in regulating non-specific inflammatory response involved in many pathological processes. The current study tested the hypothesis that myocardial infarction in patients with obesity can lead to increased production of proinflammatory cytokines and unfavorable course of the pathological process. METHODS: The study recruited 232 male patients with ST-elevated myocardial infarction. The mean age of the patients was 58.7 (52.2-69.9) years. All the patients were assigned to two groups according to the computed tomography findings: 1 (n = 160) patients with visceral obesity (VO), and 2 (n = 72) patients without VO. Interleukins were measured in blood serum on days 1 and 12 after MI. RESULTS: All patients with MI demonstrated elevated levels of proinflammatory markers and reduced anti-inflammatory markers in the in-hospital period. The results suggested that among all studied inflammatory markers IL-6 (OR 1.9; 95% CI (1.6-2.8) and CRP (OR 1.3; 95% CI (1.1-1.8) were closely related to VO. One year after MI adverse cardiovascular outcome frequently occurred in patients with VO. There were two cardiac deaths (3.1%), 6 cases (9.3%) of recurrent MI, 19 cases (29.6%) of repeated hospitalizations for unstable angina, whereas only 2 patients without VO (6.6%) were hospitalized for unstable angina. The results of the logistic regression analysis demonstrated that IL-6, IL-12, and IL-10 had the highest predictive value for occurrence of adverse cardiovascular events in patients with VO. CONCLUSION: Cytokine profile in MI patients with VO is characterized by an imbalance caused by elevated pro-inflammatory interleukins and decreased anti-inflammatory interleukins. Obesity in patients was associated with a marked increase in IL-6 and CRP levels.

Early Effects of Treatment Low-Dose Atorvastatin on Markers of Insulin Resistance and Inflammation in Patients with Myocardial Infarction.

Dyslipidemia is one of the primary causes of cardiovascular disease. Therefore, attention has been focused on the development of drugs that normalize lipid levels and exert an effect on markers of atherothrombosis, insulin resistance (IR), and inflammation. Atorvastatin is a drug with not only lipid-lowering potential, but it has multiple non-lipid effects. This study aimed to evaluate atorvastatin effects on lipid, adipokine, IR, and inflammatory statuses in patients with myocardial infarction (MI) in an in-hospital setting. This study included 66 patients with confirmed ST-segment elevation MI, who were treated with atorvastatin 20 mg/day starting on day 1 of MI, without any dose changes. The comparison group consisted of 60 patients receiving standard anti-anginal and anti-thrombotic therapy. During the hospital stay, both groups showed a reduction in total cholesterol level and free fatty acids and increased concentrations of apolipoprotein A, especially those patients receiving atorvastatin. On day 1 of MI, patients in both groups had elevated levels of leptin by 2.9- to 3.3-fold, but the leptin levels decreased by 40.3% and were significantly lower than in patients not taking statins. The treatment with atorvastatin was associated with a decrease in C-reactive protein and interleukin-6 by 23.1 and 49.2%, respectively, compared with baseline values. In the group of patients on standard therapy, there was a decrease of interleukin-6 by 31.7%. Atorvastatin administered early on during hospitalization to patients with MI contributed to the improvement of lipid, adipokine and pro-inflammatory statuses and decreased IR.

Prognostic Value of Soluble ST2 During Hospitalization for ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Studying the role of soluble ST2 (sST2) during hospitalization for myocardial infarction (MI) can be helpful for predicting the course of the hospitalization and development of complications. METHODS: We included 88 patients with MI (median age, 58 yr). Depending on the course of the hospitalization, the patients were divided into two groups: the favorable (n=58) and unfavorable (n=30) outcome groups. On days 1 and 12 after MI, serum sST2 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured by ELISA. RESULTS: On day 1, the concentrations of sST2 and NT-proBNP increased 2.4- and 4.5-fold, compared with the controls. Measurements on day 12 showed a significant decrease in the sST2 level (P=0.001), whereas the NT-proBNP level did not change. On day 1, the sST2 level in the unfavorable outcome group was 2-fold higher than that in the favorable outcome group and 3.7-fold higher than in the controls. On day 12, the marker level decreased in both groups. On day 1, the NT-proBNP level in the unfavorable outcome group was 6.8-fold higher than in the controls and 1.8-fold higher than in the favorable outcome group. On day 12, the level of NT-proBNP remained elevated in both groups. Determining the levels of both sST2 and NT-proBNP increases their diagnostic significance (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.7-3.2; areas under curve [AUC] 0.89; P=0.004). CONCLUSIONS: The level of sST2 is a more sensitive indicator during MI hospitalization than NT-proBNP.

The role of adipose tissue and adipokines in the manifestation of type 2 diabetes in the long-term period following myocardial infarction.

BACKGROUND: This study aimed to evaluate the markers of insulin resistance and adipokine status in patients with visceral obesity during hospitalization following myocardial infarction (MI) and assess the disturbances of carbohydrate metabolism present 1 year after MI onset. METHODS: 94 male patients with MI were recruited. The exclusion criteria were as follows: age less than 50 or greater than 80 years, the presence of type 2 diabetes mellitus (T2DM), and a prior history of pronounced renal failure.Obesity types were defined according to body mass index (BMI), waist circumference (WC) and visceral adipose tissue (VAT) area. Glucose, insulin, adiponectin, leptin, and insulin resistance (IR) index were measured on days 1 and 12 after the onset of MI. New-onset type 2 diabetes was assessed 1 year after MI onset. RESULTS: According to computed tomography assessments of all study patients, 69 % of patients with MI suffered from visceral obesity. The VAT area was more closely associated with the risk of developing type 2 diabetes compared with the obesity parameters, BMI and WC. Patients with a VAT area greater than 130 cm(2) had a 3.6-fold higher risk of developing type 2 diabetes. The presence of IR and hyperleptinemia increased the risk of developing diabetes in the post-MI period 3.5 and 3.7 times, respectively, in patients with visceral obesity compared with patients without visceral obesity. CONCLUSION: Visceral obesity is associated with IR, a 5.7-fold increase in leptin levels and a high risk of developing type 2 diabetes 1 year after MI onset.