Background and objectives: Mechanical stress is currently considered as the main factor promoting calcific aortic valve stenosis (AS) onset. It causes endothelial damage and dysfunction. The chronic inflammatory process causes oxidative stress. Oxidative stress-induced high-density lipoprotein cholesterol (HDL-C) dysfunction is an important component of the development of AS. The aim of the study was to evaluate the role of HDL-C in AS patients in three severity grades and in relation to the biomarkers of oxidative stress, thioredoxin reductase 1 (TrxR1) and myeloperoxidase (MPO). Materials and Methods: 18 patients with mild, 19 with moderate. and 15 with severe AS were included in the study, and 50 individuals were enrolled in the control group. Stenosis severity was determined by echocardiography. The TrxR1 and MPO were analyzed by ELISA, and HDL-C by commercially available tests. Data were analyzed using GraphPad Prism 8. Results: HDL-C in AS patients vs. control substantially decreases and this decline was observed in all three AS severity groups: mild (p = 0.018), moderate (p = 0.0002), and severe (p = 0.004). In both the control and the stenosis group, the HDL-C was higher in women than in men. In comparison to control, the HDL-C level was lower in the AS group, and more pronounced in women (p = 0.0001) than in men (p = 0.049). A higher TrxR1 level was observed in patients with mild (p = 0.0001) and severe AS (p = 0.047). However, a clear correlation between TrxR1 and HDL-C was not obtained. Analysis of MPO showed differences in all severity grades vs. control (p = 0.024 mild stenosis; p = 0.002 moderate stenosis; p = 0.0015 severe stenosis). A negative correlation (p = 0.047; rp = −0.28) was found between MPO and HDL-C, which confirms the adverse effects of MPO resulting in HDL-C dysfunction. Conclusions: In this study, we justified HDL-C level association with AS development process. The results unequivocally substantiated the association between HDL-C and AS in all severity grades in women, but only in moderate AS for men, which we explained by the small number of men in the groups. The obtained correlation between the HDL-C and MPO levels, as well as the concurrent decrease in the HDL-C level and increase in the TrxR1 level, indicate in general an HDL-C association with oxidative stress in AS patients.

Background and Objectives: Aortic valve stenosis (AS) develops with a pronounced local inflammatory response, where a variety of growth factors are involved in the process, and may have a pro-inflammatory and anti-inflammatory effect. The aim of our study was to elucidate whether circulating growth factors: growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), and fibroblast growth factor 21 (FGF-21) could be proposed as clinically relevant biomarkers to improve risk stratification in AS patients. Materials and Methods: AS patients were classified into three groups: 16 patients with mild AS stenosis; 19 with moderate and 11 with severe AS, and 30 subjects without AS (echocardiographically approved) were selected as a control group. GDF-15, Ang-2, VEGF-A, FGF-2, and FGF-21 were measured in plasma by the ELISA method. Results: GDF-15 levels differed significantly not only when comparing AS patients with control groups (p < 0.0001), but also a statistically significant difference was achieved when comparing AS patients at a mild degree stage with control individuals. We found a strong relationship of GDF-15 levels regarding AS severity degree (p < 0.0001). VEGF-A, FGF-2 and FGF-21 levels were significantly higher in AS patients than in controls, but relationships regarding the AS severity degree were weaker (p < 0.02). ROC analysis of the study growth factors showed that GDF-15 might serve as a specific and sensitive biomarker of AS stenosis (AUC = 0.75, p = 0.0002). FGF-21 correlated with GDF-15, Ang-2, and FGF-2, but it did not reach the level to serve as a clinically relevant biomarker of AS stenosis. Conclusions: AS is associated with significantly increased GDF-15, VEGF-A, FGF-2, and FGF-21 levels in plasma, but only GDF-15 shows a pronounced relationship regarding AS severity degree, and GDF-15 might serve as a specific and sensitive biomarker of AS stenosis.

ANNOTATIONCalcific stenosis of the aortic valve (AVS) manifests with fibro-calcific remodelation (transformation) of the aortic valve (AV), which is a slow process of chronic inflammation and calcification with completely unexplored and ambiguous etiology and pathogenesis.Currently, there is no medical treatment to stop or delay the progression of the disease.The only treatment available is a surgical replacement of AV or transcathether aortic valve implantation. With increasing people's survival the number of patients with clinically relevant AVS is increasing.Almost in 25% of people after the age of 65 echocardiographically AV sclerosis is found and about 17% of these people further develop AVS. The time between diagnosis of AV sclerosis and development of severe AVS is on average 6-8 years.The aim of the research work is to analyze and find out which factors involved in the inflammation and calcification process, cell-produced regulatory molecules (cytokines) affect AVS development in all three AVS severity degrees and to what extent. As a result, some biomarkers could be isolated to predict the rate of progression of AVS. Cell-produced regulatory molecules (cytokines) were detected in blood serum and plasma (thioredoxin reductase-1, mieloperoxidase).The interaction of oxidative stress and inflammation in all three AVS severity degrees was analyzed during the research work. The direct and indirect effects of total cholesterol and its fractions on the development of AVS were also re-evaluated.The conducted clinical-analytical study is a prospective case-control study of mixed type. 102 patients were selected voluntarily according to inclusion and exclusion criteria and divided into two basic groups: the control group and the AVS group. Individuals in the control group were included according to an echocardiographically approved healthy aortic valve between the age of 50 to 80 years, which corresponds to the AVS patients' age at the 2012 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery Guidelines for the management of valvular heart disease. Patients of the AVS group were divided into three subgroups according to the degree of the AV stenosis, based on the 2012 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery Guidelines for the Management of Valvular Heart Disease.In the study for the first time in the Latvia population, inflammatory and noninflammatory factors, cell-produced regulatory molecules (cytokines) in blood serum and plasma were analyzed. The obtained results were compared between the control group and all three AVS grades. 3 Knowing recent studies on etiopathogenesis of the calcific AVS, inflammatory and noninflammatory factors (chemerin, FGF-21, TrxR1 and MPO) that have not been studied in AVS patients so far were identified.The obtained results provide more complete information on the pathogenesis of AVS and the correlation between the analyzed inflammatory and non-inflammatory factors. The relationship between chemerin...

The aim of the present study was to evaluate plasma levels of chemerin, myeloperoxidase (MPO), fibroblast growth factor-21 (FGF-21), thioredoxin reductase-1 (TrxR1), and matrix metallopeptidase-9 (MMP-9) in acquired aortic valve (AoV) stenosis patients to determine correlations between the studied cellular factors, and also clarify the predictive values of these factors as biomarkers in AoV stenosis. AoV stenosis patients were classified into three groups: 17 patients with mild AoV stenosis; 19 with moderate and 15 with severe AoV stenosis. Twenty-four subjects without AoV stenosis were selected as a control group. Our findings suggest that AoV stenosis might be associated with increased chemerin, TrxR1, MPO, and FGF-21 levels in plasma. Moreover, these factors and also MMP-9 already reached statistically significantly elevated levels in the early stages of AoV stenosis, but MPO levels were more pronounced in patients with moderate and severe AoV stenosis. Chemerin was correlated with all of the studied cytokines; TrxR1 and MMP-9 were correlated with several other cellular factors. Our findings (by ROC analysis) suggest that MPO and chemerin might serve as specific and sensitive biomarkers for AoV stenosis without grading the severity, but, in relation to mild AoV stenosis, TrxR1, FGF-21, and MMP-9 also reached good or moderate levels as biomarkers. The cellular factors might serve as novel diagnostic and prognostic biomarkers in AoV stenosis patients, while chemerin and MPO may be more powerful.