Proteomic Profiling of Endothelial Cells Exposed to Mitomycin C: Key Proteins and Pathways Underlying Genotoxic Stress-Induced Endothelial Dysfunction.

Mitomycin C (MMC)-induced genotoxic stress can be considered to be a novel trigger of endothelial dysfunction and atherosclerosis-a leading cause of cardiovascular morbidity and mortality worldwide. Given the increasing genotoxic load on the human organism, the decryption of the molecular pathways underlying genotoxic stress-induced endothelial dysfunction could improve our understanding of the role of genotoxic stress in atherogenesis. Here, we performed a proteomic profiling of human coronary artery endothelial cells (HCAECs) and human internal thoracic endothelial cells (HITAECs) in vitro that were exposed to MMC to identify the biochemical pathways and proteins underlying genotoxic stress-induced endothelial dysfunction. We denoted 198 and 71 unique, differentially expressed proteins (DEPs) in the MMC-treated HCAECs and HITAECs, respectively; only 4 DEPs were identified in both the HCAECs and HITAECs. In the MMC-treated HCAECs, 44.5% of the DEPs were upregulated and 55.5% of the DEPs were downregulated, while in HITAECs, these percentages were 72% and 28%, respectively. The denoted DEPs are involved in the processes of nucleotides and RNA metabolism, vesicle-mediated transport, post-translation protein modification, cell cycle control, the transport of small molecules, transcription and signal transduction. The obtained results could improve our understanding of the fundamental basis of atherogenesis and help in the justification of genotoxic stress as a risk factor for atherosclerosis.

Expression of Ceramide-Metabolizing Enzymes in the Heart Adipose Tissue of Cardiovascular Disease Patients.

Here, we examined the expression of ceramide metabolism enzymes in the subcutaneous adipose tissue (SAT), epicardial adipose tissue (EAT) and perivascular adipose tissue (PVAT) of 30 patients with coronary artery disease (CAD) and 30 patients with valvular heart disease (VHD) by means of quantitative polymerase chain reaction and fluorescent Western blotting. The EAT of patients with CAD showed higher expression of the genes responsible for ceramide biosynthesis (SPTLC1, SPTLC2, CERS1, 5, 6, DEGS1, and SMPD1) and utilization (ASAH1, SGMS1). PVAT was characterized by higher mRNA levels of CERS3, CERS4, DEGS1, SMPD1, and ceramide utilization enzyme (SGMS2). In patients with VHD, there was a high CERS4, DEGS1, and SGMS2 expression in the EAT and CERS3 and CERS4 expression in the PVAT. Among patients with CAD, the expression of SPTLC1 in SAT and EAT, SPTLC2 in EAT, CERS2 in all studied AT, CERS4 and CERS5 in EAT, DEGS1 in SAT and EAT, ASAH1 in all studied AT, and SGMS1 in EAT was higher than in those with VHD. Protein levels of ceramide-metabolizing enzymes were consistent with gene expression trends. The obtained results indicate an activation of ceramide synthesis de novo and from sphingomyelin in cardiovascular disease, mainly in EAT, that contributes to the accumulation of ceramides in this location.

IL18-family Genes Polymorphism Is Associated with the Risk of Myocardial Infarction and IL18 Concentration in Patients with Coronary Artery Disease.

BACKGROUND: Atherogenesis is mainly determined by endothelial dysfunction, lipid metabolism disorders and inflammation. The atherogenesis-related inflammatory process is a complex interaction between serum blood lipoproteins, inflammatory cells, endothelial and smooth muscle cells and extracellular matrix; the role of chronic inflammation in atherogenesis was proposed. MATERIAL AND METHODS: A pathogenetic role of polymorphism in NF-kB pathway genes in coronary artery disease and associated pathological conditions has been suggested in a case-control retrospective study. 260 coronary artery disease patients permanently living in a large industrial region of Russian Federation (Kemerovo region) were recruited in the study. We examined nine single nucleotide polymorphisms in IL18, IL18R1 and IL18RAP genes by polymerize chain reaction; and serum blood level of IL18 by enzyme-linked immunosorbent assay. RESULTS: Polymorphic variants rs13015714 (IL18R1) and rs917997 (IL18RAP) are associated with the risk of myocardial infarction and high serum levels of IL18. Minor alleles of rs13015714 and rs917997 sites are associated with high risk of developing multifocal atherosclerosis and arterial hypertension in patients with stable coronary artery disease after myocardial infarction. CONCLUSIONS: Thus, polymorphism in the genes of IL18 receptor is determine the IL18 contents and important in the development of coronary atherosclerosis, associated pathological conditions and the risk of acute coronary events; prospective monitoring of patients with early clinical signs of adverse events is required to confirm the role of IL18, IL18R1, and IL18RAP genes polymorphism in atherogenesis.

[Frailty syndrome as an independent predictor of adverse prognosis in patients with chronic heart failure].

This review presents results of clinical studies of senile asthenia ("fragility") syndrome and chronic heart failure (CHF). Recent reports of the "fragility" prevalence in patients with CHF are described. The review presents specific features of pathophysiological pathways underlying the development of both senile asthenia syndrome and CHF; the role of "fragility" in the progression and complications of CHF is addressed. Senile asthenia syndrome associated with CHF is regarded as an independent predictor of unfavorable prognosis and high mortality in this patient category. The authors concluded that methods for "fragility" evaluation in CHF patients followed by risk stratification and selection of individual management tactics should be implemented in clinical practice.

Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Randomized Clinical Trial of Surgical vs. Percutaneous vs. Hybrid Revascularization in Multivessel Coronary Artery Disease: Residual Myocardial Ischemia and Clinical Outcomes at One Year-Hybrid coronary REvascularization Versus Stenting or Surgery (HREVS).

AIM: Optimal revascularization strategy in multivessel (MV) coronary artery disease (CAD) eligible for percutaneous management (PCI) and surgery remains unresolved. We evaluated, in a randomized clinical trial, residual myocardial ischemia (RI) and clinical outcomes of MV-CAD revascularization using coronary artery bypass grafting (CABG), hybrid coronary revascularization (HCR), or MV-PCI. METHODS: Consecutive MV-CAD patients (n = 155) were randomized (1 : 1 : 1) to conventional CABG (LIMA-LAD plus venous grafts) or HCR (MIDCAB LIMA-LAD followed by PCI for remaining vessels) or MV-PCI (everolimus-eluting CoCr stents) under Heart Team agreement on equal technical and clinical feasibility of each strategy. SPECT at 12 months (primary endpoint of RI that the trial was powered for; a measure of revascularization midterm efficacy and an independent predictor of long-term prognosis) preceded routine angiographic control. RESULTS: Data are given, respectively, for the CABG, HCR, and MV-PCI arms. Incomplete revascularization rate was 8.0% vs. 7.7% vs. 5.7% (p=0.71). Hospital stay was 13.8 vs. 13.5 vs. 4.5 days (p < 0.001), and sick-leave duration was 23 vs. 16 vs. 8 weeks (p < 0.001). At 12 months, RI was 5 (2, 9)% vs. 5 (3, 7)% vs. 6 (3, 10)% (median; Q1, Q3) with noninferiority p values of 0.0006 (HCR vs. CABG) and 0.016 (MV-PCI vs. CABG). Rates of angiographic graft stenosis/occlusion or in-segment restenosis were 20.4% vs. 8.2% vs. 5.9% (p=0.05). Clinical target vessel/graft failure occurred in 12.0% vs. 11.5% vs. 11.3% (p=0.62). Major adverse cardiac and cerebral event (MACCE) rate was similar (12% vs. 13.4% vs. 13.2%; p=0.83). CONCLUSION: In this first randomized controlled study comparing CABG, HCR, and MV-PCI, residual myocardial ischemia and MACCE were similar at 12 months. There was no midterm indication of any added value of HCR. Hospital stay and sick-leave duration were shortest with MV-PCI. While longer-term follow-up is warranted, these findings may impact patient and physician choices and healthcare resources utilization. This trial is registered with NCT01699048.

Genetic forms and pathophysiology of essential arterial hypertension in minor indigenous peoples of Russia.

BACKGROUND: To study the genetic forms and pathophysiology of arterial hypertension by evaluating plasma renin activity in the Shors, minor indigenous peoples inhabiting the south of Western Siberia. METHODS: A single-stage study of indigenous (the Shors) and non-indigenous peoples living in the villages of Gornaya Shoria of the Kemerovo region in the south of Western Siberia was conducted in the period from 2013 to 2017. One thousand four hundred nine adults (901 Shors and 508 non-indigenous inhabitants) were recruited in the study using a continuous sampling plan. Arterial blood pressure was measured according to 2018 ESC/ESH guidelines for the management of arterial hypertension. All the respondents underwent clinical and instrumental examination. Plasma renin activity was determined by enzyme-linked immunoassay with the BRG kits (Germany). Polymorphisms of ACE (I/D, rs 4340), АGT (c.803 T > C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A > G, Ser49Gly, rs1801252) and ADRA2B (I/D, rs 28,365,031) genes were tested using polymerase chain reaction. RESULTS: Renin-dependent hypertensive patients prevailed in both ethnic groups (65.6% in the indigenous group vs. 89.8% in the non-indigenous group, p = 0.001). Prevalence of a volume-dependent AH was low in both groups (34.4% in the indigenous group vs. 10.2% in the non-indigenous group, р = 0.001). The D/D and Т/Т genotypes of the АСЕ [OR = 6.97; 95% CI (1.07-55.58)] and AGT [OR = 3.53; 95% CI (1.02-12.91)] genes were associated with the renin-dependent AH in the Shors. The C/C genotype of AGTR1 gene was found to predispose to the volume-dependent AH [OR = 5.25; 95% CI (1.03-27.89)]. The C/C genotype of AGTR1 gene was associated with moderate or high renin levels suggesting essential AH in the non-indigenous group [OR = 5.00; 95% CI (1.21-22.30), р = 0.029]. CONCLUSION: An in-depth understanding of AH pathophysiology and its genetic forms ensures the optimal choice of blood pressure-lowering treatment and optimizes AH control.

[Efficiency of pharmacogenetic approach to anticoagulant therapy in patients with prosthetic heart valves].

BACKGROUND: This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range. AIMS: We determined the clinical outcome of the pharmacogenetic approach at the start of warfarin therapy in patients with prosthetic heart valves. MATERIALS AND METHODS: The study included 915 patients, of which 512 women and 403 men (mean age 56±10 years), living in Western Siberia. Rheumatic heart disease was the main diagnosis that caused the acquired defect. Mechanical prostheses were used in 70% of cases of cardiac surgery. Real-time polymerase chain reaction used for molecular genetic testing. RESULTS: The frequencies of the alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasoid populations. The use of pharmacogenetic testing results at the beginning of warfarin therapy reduced the time required for selecting a therapeutic dose of anticoagulant by 2 times and increased the duration of stay in the INR therapeutic range by 20.2%. CONCLUSION: The use of the pharmacogenetic approach at the begin­ ning of warfarin therapy contributes to the effectiveness and safety of anticoagulant therapy in this category of patients.

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.

EEG and Clinical Factors Associated with Mild Cognitive Impairment in Coronary Artery Disease Patients.

BACKGROUND: Although an impaired cognitive status in patients with coronary artery disease (CAD) is not rare, the neurophysiological and clinical indicators of mild cognitive impairment (MCI) have been insufficiently investigated so far. METHODS: EEG and neuropsychological testing as well as clinical examination were performed on 122 patients with CAD, who were divided into two groups, those with MCI (n = 60; mean age 57.4 ± 5.81 years) and those without MCI (n = 62; mean age 57.0 ± 5.04 years). Binary logistic regression was used to identify the relationship between EEG and clinical variables and the probability of MCI. RESULTS: Higher theta/alpha ratios, theta1 rhythm power with closed eyes in the frontal and occipital areas of the left hemisphere, and alpha2 rhythm power with eyes open in the frontal areas of the right hemisphere were associated with an increased risk for MCI in CAD patients. A low educational level, type 2 diabetes mellitus, and severe coronary lesions according to the SYNTAX Score (≥23 points) increased the risk for MCI as well. CONCLUSIONS: The findings of our study show that a theta activity increase in frontal and occipital sites, as well as high theta/alpha ratios, may be considered as the earliest EEG markers of vascular cognitive disorders.

Localization of fat depots and cardiovascular risk.

Despite the existing preventative and therapeutic measures, cardiovascular diseases remain the main cause of temporary disability, long-term disability, and mortality. Obesity is a major risk factor for cardiovascular diseases and their complications. However, not all fat depots have the same inflammatory, paracrine, and metabolic activities. In addition, recent studies have indicated that the accumulation of visceral fat, rather than subcutaneous fat, is associated with increased cardiometabolic risk. However, there is also evidence that increasing the area of visceral fat can help protect against lipotoxicity. This review aims to discuss the contemporary literature regarding the characteristics of the visceral, epicardial, and perivascular fat depots, as well as their associations with cardiovascular disease.

A comparison of the genetic and clinical risk factors for arterial hypertension between indigenous and non-indigenous people of the Shoria Mountain Region.

BACKGROUND: This study investigated the non-genetic and genetic risk factors for arterial hypertension (AH) in two ethnic groups living in the Mountain Shoria region: Shors and non-indigenous people. METHODS: Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older). RESULTS: The prevalence of AH was lower in Shors (39.9% vs. 46.1%), mainly due to differences between men from the different groups: 33.2% vs. 45.8%. The percentage of people with AH, overweight, and obesity (including transabdominal obesity) in the different age groups did not differ between ethnicities. We identified statistically significant differences in the prevalence of hypertension according the two ethic groups according to age, body weight, and abdominal obesity. I/D ACE and ADRA2B polymorphisms were associated with AH. In DD ACE and DD ADRA2B carriers, there were fewer hypertensive patients in Shors than in non-indigenous people: 40.6% vs. 58.6% and 38.3% vs. 64.0%, respectively. In DD ACE carriers, more Shors had AH (60.0% vs. 37.1%). CONCLUSION: Among Shors, the following factors increased AH risk: female sex, age, hypercholesterolemia, hyperbetacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), glucose intolerance, and the DD ACE, CT MTHFR, and AA ADRB1 genotypes; among the non-indigenous population, the main factors were age, hypercholesterolemia, hyperbetacholesterinemia, hypoalfacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), and ID ACE genotype.

Endovascular Interventions Permit Isolation of Endothelial Colony-Forming Cells from Peripheral Blood.

BACKGROUND: Isolation of endothelial colony-forming cells (ECFCs) is difficult due to the extremely low concentration of their precursors in the peripheral blood (PB). We hypothesized that mechanical injury to the arterial wall during percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) may increase the release of circulating ECFC precursors and induce their growth in vitro. METHODS: PB samples from patients with coronary artery disease were collected before, immediately after, and 24 h after the surgery in the CABG group. In the PCI group, PB was isolated before, immediately after the insertion of the catheter, immediately after balloon angioplasty, and 24 h after the PCI. A mononuclear fraction of PB was isolated and differentiated into ECFCs with the following immunophenotyping and evaluation of angiogenic properties. RESULTS: The obtained cultures corresponded to the phenotype and tube forming potential consistent with ECFCs. The isolation of ECFCs in the PCI group was successful in 75% of cases (six out of eight patients) after catheter insertion and in 87.5% (seven out of eight patients) after the balloon inflation and stent deployment. These cultures had high/medium proliferative activity in contrast to those obtained before or 24 h after the intervention. CONCLUSIONS: Mechanical injury during PCI increases the release of ECFC precursors to the PB and, hence, the efficacy of ECFC isolation.

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.

Serum neutrophil gelatinase-associated lipocalin has an advantage over serum cystatin C and glomerular filtration rate in prediction of adverse cardiovascular outcome in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RESULTS: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. CONCLUSIONS: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.

Glucose levels as a prognostic marker in patients with ST-segment elevation myocardial infarction: a case-control study.

BACKGROUND: Patients with myocardial infarction (MI) have a high mortality. Therefore, new risk markers and predictors of an adverse outcome for MI are required. The role of hyperglycemia in the development of cardiovascular complications in MI patients is still unclear. METHODS: A total of 529 consecutive patients with the diagnosis of ST-segment elevation acute coronary syndrome within 24 h of the onset of symptoms were included in the study. All of the patients underwent blood glucose measurement at admission to hospital. The glycemic profile, including measurement of blood glucose levels early in the night and in the morning (3 a.m. and 5 a.m.), was assessed in 77 patients with diabetes on days 6-10 of the course of MI to monitor the efficiency of blood glucose-lowering therapy and to detect hypoglycemic episodes. RESULTS: In-hospital mortality showed relationship between the level of blood glucose on admission and in-hospital mortality in patients with MI with ST-segment elevation in combination with diabetes mellitus. There was a direct linear relationship between blood glucose levels and in-hospital mortality in patients without diabetes. CONCLUSION: Episodes of hypoglycemia recorded in MI patients with diabetes in the hospital stage of treatment do not determine the prognosis, but enable identification of patients with an unfavorable course in the postinfarction period.

Conjugation with RGD Peptides and Incorporation of Vascular Endothelial Growth Factor Are Equally Efficient for Biofunctionalization of Tissue-Engineered Vascular Grafts.

The blend of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(ε-caprolactone) (PCL) has recently been considered promising for vascular tissue engineering. However, it was shown that PHBV/PCL grafts require biofunctionalization to achieve high primary patency rate. Here we compared immobilization of arginine-glycine-aspartic acid (RGD)-containing peptides and the incorporation of vascular endothelial growth factor (VEGF) as two widely established biofunctionalization approaches. Electrospun PHBV/PCL small-diameter grafts with either RGD peptides or VEGF, as well as unmodified grafts were implanted into rat abdominal aortas for 1, 3, 6, and 12 months following histological and immunofluorescence assessment. We detected CD31⁺/CD34⁺/vWF⁺ cells 1 and 3 months postimplantation at the luminal surface of PHBV/PCL/RGD and PHBV/PCL/VEGF, but not in unmodified grafts, with the further observation of CD31⁺CD34-vWF⁺ phenotype. These cells were considered as endothelial and produced a collagen-positive layer resembling a basement membrane. Detection of CD31⁺/CD34⁺ cells at the early stages with subsequent loss of CD34 indicated cell adhesion from the bloodstream. Therefore, either conjugation with RGD peptides or the incorporation of VEGF promoted the formation of a functional endothelial cell layer. Furthermore, both modifications increased primary patency rate three-fold. In conclusion, both of these biofunctionalization approaches can be considered as equally efficient for the modification of tissue-engineered vascular grafts.

Decreased Cathepsin K Plasma Level may Reflect an Association of Osteopoenia/Osteoporosis with Coronary Atherosclerosis and Coronary Artery Calcification in Male Patients with Stable Angina.

BACKGROUND: The aim of this study was to evaluate the plasma levels of bone turnover markers (BTMs) in male patients with stable angina depending on the bone mineral density (BMD), coronary atherosclerosis (CA) and coronary artery calcification (CAC). METHODS: We recruited 112 males with verified stable angina. All the patients underwent coronary angiography, multislice spiral computed tomography, and dual-energy X-ray absorptiometry. Plasma levels of BTMs were measured by enzyme-linked immunosorbent assay. RESULTS: Osteopoenia and osteoporosis were reported in 90 (80.4%) and 34 (30.4%) patients, respectively. Multivessel coronary artery disease, severe CA and CAC, decreased cathepsin K plasma level, and increased osteocalcin plasma level were significantly more prevalent in patients with osteopoenia/osteoporosis compared to the subjects with normal BMD. Patients with severe CA and CAC had significantly reduced cathepsin K plasma levels. CONCLUSIONS: We revealed a significant association of osteopoenia/osteoporosis with severe CA and CAC in males with stable angina. Cathepsin K and osteocalcin plasma levels may be suggested as the significant markers of osteopoenia/osteoporosis. In addition, cathepsin K plasma level can be also a valuable marker of severe CA and CAC.

The role of cystatin C in the prognosis of adverse outcomes after the coronary artery bypass graft surgery during hospitalisation.

BACKGROUND: This study has been aimed to assess clinical significance of cystatin C in the prognosis of a risk of hospital complications among the patients with coronary artery disease CAD who have undergone coronary artery bypass surgery (CABG). METHODS: We have recruited 719 consecutive Caucasian (Russian) patients who underwent CABG in 2011-2012. RESULTS: No statistically significant differences in the serum creatinine concentration (sCr) and glomerular filtration rate before and seven days after the surgery have been found among the patients belonging to different EuroSCORE risk groups. A statistically significant elevation of serum cystatin C concentration (sCC) before and seven days after the surgery has been demonstrated in EuroSCORE medium- and high-risk groups in comparison with the low-risk group. In addition, we have revealed increased pre-surgical levels of sCC in patients who had died earlier than seven days after CABG. Regarding the cardiovascular complications, a statistically significant elevation of sCC has been observed in patients with and without myocardial infarction (MI), stroke, or acute kidney injury (AKI) in the postoperative period. CONCLUSIONS: We suggest that the determination of sCC before and after CABG surgery may help in the prognosis of adverse cardiovascular and renal outcomes after the CABG surgery.

Microalbuminuria and prediction of cardiovascular complications in patients with coronary artery disease and type 2 diabetes mellitus after CABG surgery.

BACKGROUND: This investigation was aimed at assessing the clinical significance of microalbuminuria (MA) in predicting in-hospital adverse outcomes amongst the patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who have undergone coronary artery bypass graft (CABG) surgery. METHODS: We recruited 720 consecutive Caucasian (Russian) patients who underwent CABG surgery during 2011-2012. RESULTS: Patients with renal dysfunction (RD) and without type 2 DM had significantly higher median serum creatinine seven days after CABG surgery compared to patients without RD and type 2 DM. There were no statistically significant intergroup differences regarding glomerular filtration rate. However, the highest median of urine albumin excretion 24hours before and seven days after CABG surgery was detected in patients with RD and type 2 DM whilst the lowest median was noted in patients without RD and type 2 DM. Median of urine albumin excretion 24hours before and seven days after CABG surgery in patients with adverse outcome was significantly higher compared to patients with a favourable outcome. CONCLUSIONS: We suggest that the determination of MA before and after CABG surgery may assist in predicting adverse outcomes after CABG surgery.