Introduction. Infective endocarditis (IE) is a bacterial disease with frequent pathogen localization on the heart valve apparatus. IE is characterized by rapid development of heart failure and frequent thromboembolic complications (TEC). IE features are accounted for by foreign pathogen nature and state of human immune system (IS). The imbalanced IS in infective endocarditis is manifested by impaired cytokine-mediated interactions. This confirms the rationality of studying cytokines to advance understanding of the pathogenesis for various conditions. Most cytokine genes are characterized by polymorphism and existing isoforms underlying disease predisposition. Genetic polymorphism of vascular endothelial growth factor A (VEGF-A) plays an important role in the induction of vasculogenesis and angiogenesis. The pathogenetic VEGF role in IE has not been thoroughly studied. Research objective analysis of polymorphic nucleotide sequence variants in the vascular endothelial growth factor gene, taking into account a relation with its serum concentration in patients with infective endocarditis. Materials and methods. 86 patients treated with verified diagnosis of infective endocarditis at the Scientific Research Institute Regional Clinical Hospital No. 1 of Krasnodar were divided into two clinical groups in accordance with the IE course: Group 1 IE with TEC (n = 44), group 2 IE without TEC (n = 42), and the control group consisted of 20 apparently healthy individuals. The concentration of serum VEGF-A (pg/mL) was measured by ELISA on day 1 of hospitalization. Genomic DNA was isolated from whole blood leukocytes and used to determine the frequency of genotypes of VEGF gene polymorphic variants. Results. Significant differences in the frequency distribution of VEGF-rs2010963 genotypes between patients with infective endocarditis and control group were revealed: G/G (OR = 0.25; p = 0.012) and G/C (OR = 4.28; p = 0.022), as well as differences between VEGF concentrations for various SNP-rs2010963 genotypes (p = 0.0001). A study of VEGF genotype frequency distribution between patients of clinical groups showed a significantly decreased frequency of the genotype G/G (rs2010963) in the IE group with TEC (OR = 0.21; p = 0.014) and increased frequency of G/C (OR = 4.72; p = 0.024) compared with the control group, whereas in patients with IE without TEC, significant (p = 0.0003) differences in serum concentrations of VEGF-rs2010963 were found in accordance with genotypes GG/CC (p = 0.01) and GG/GC (p = 0.003). Conclusion. The relationship between the VEGF genotypes (G/G and G/C of rs2010963 polymorphism) and related serum concentration among patients with IE was revealed. Carriers of the minor C allele (rs2010963) had higher serum VEGF levels. The results obtained complement and systematize current scientific data on the disease pathogenesis, as well as focus on the genetic determinant of the developing complications.
Abstract. Introduction. Infective endocarditis is a bacterial disease. Pathogen is localized mainly on heart valves and endocardium. This condition is accompanied by immunopathological manifestations and potential generation of septic process being unfavorable prognosis for disease outcome. Currently, the causes of death of patients with endocarditis have been increasingly presented as thromboembolic complications, which severity depends on variant of the disease course. An important role in imbalanced immune system in the infectious process is assigned to altered intercellular interaction mediated via cytokine network. Activated immune cells produce cytokines, which investigating is important in terms of interpreting changes in immune system functionality, assessing the severity of diseases and controlling therapeutic effectiveness. Infective endocarditis remains a severe disease associated with high mortality despite current advances in diagnostics and treatment. A timely diagnostic process and early initiation of treatment are major factors for successful patient management necessitating to improve diagnostics of various clinical variants of endocarditis course, taking into account pathogenetically relevant cytokines. Objective – to comparatively evaluate importance of serum cytokine concentrations in patients with uncomplicated course of infective endocarditis and its thromboembolic complications and determine cytokine markers of various variants of endocarditis course. Materials and methods. An immunological examination of 119 blood serum samples from patients with confirmed diagnosis of infectious endocarditis and 20 samples from apparently healthy persons was carried out. Depending on the clinical disease form, the patients were divided into 4 groups: group 1 – primary infective endocarditis (PIE) with thromboembolic complications (n=24), 2 – PIE without thromboembolic complications (n=34), 3 – secondary IE with thromboembolic complications (n=27), 4 – secondary IE without thromboembolic complications (n=34). The control group consisted of 20 apparently healthy subjects. Immunological studies of serum cytokine concentrations were conducted in all groups. Results. Statistically significant increase in serum concentration of IL-10, IL-6, VEGF-A, IL-18, IL-1Ra and IL-8 was revealed in all clinical groups of patients compared to those in control group (p0,05). By correlation analysis, we found a significant positive relationship between IL-10 and IL-18 or IL-6. An increase in the concentration of IL-10 leads to increased level of pro-inflammatory IL-18 and IL-6. The marker of secondary endocarditis was observed as increased level of serum concentrations of IFN-γ. A characteristic feature of primary infective endocarditis with thromboembolic complications was revealed as significantly increased serum concentration of IL-8, IL-1Ra and IL-6. Markers of secondary complicated endocarditis were identified as increased level of IL-6, VEGF-A and IL-18.
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