26. Chronic periodontitis and endothelial dysfunction In patients with arterial hypertension

The work offers a view at the data obtained through an examination of 120 patients with chronic generalized periodontitis (CP) and arterial hypertension (AH). The check-up included clinical examination, immunohistochemical, morphometric studies, as well as evaluation of the endothelium vasodilating function. CP in patients with hypertension features more significant changes in the quantitative density of gum cells positive to ET-1, endothelial NO-synthase, if compared to the CP values in patients with no background somatic pathology. Changes affecting vasoactive mediators in the gum are associated with a systemic inflammatory response and a violation of the endothelium vasodilating function. Periodontitis remission can be achieved with the therapy of the neurotransmitter imbalance.

Specificity of blood pressure numbers in Holter monitoring depending on gene polymorphism among residents of Ternopil region afflicted with essential arterial hypertension

The aim of this work is to determine specificities of blood pressure (BP) numbers during the day depending on polymorphism of the A1166C-gene of angiotensin II receptor type I and T786C-promoter of the endothelial NO-synthase gene among residents of Ternopil region afflicted with essential arterial hypertension.We have examined 86 patients with arterial hypertension who were treated and examined in the therapeutic department of the Central District Hospital in Kozova, aged from 45 to 76 years. All patients were measured for body weight and height, office blood pressure; also they were checked by Holter monitoring and electrocardiography (ECG), as well as examined for polymorphism of endothelial NO synthase genes and angiotensin II type 1 receptor genes. Statistical processing of the obtained data was performed with the help of the analytics software package including Statistica 8.0 (StatSoft Inc., USA) and Microsoft Office Excel-2003.The research revealed that patients with CC genotype A1166C-gene of angiotensin II receptor of the first type had a significantly higher level of systolic blood pressure (SBP) and diastolic blood pressure (DBP) – average numbers per 24 hours, day and night – compared to patients with genotype AA(p<0,05). Hereby, no significant distinctions in blood pressure variability were found.Patients with CC of the T786C promoter of the eNOs gene had higher SBP and DBP values at all times of the day compared to individuals with the TT genotype (p <0.05). Increased levels of variability of DBP during the day, as well as SBP and DBP at night, were observed among patients with CC genotype, as compared with the control group (p <0.05).Among patients with C-allele of both studied genes, there’s a high frequency of circadian rhythm disorders with predominance of the “non-dippers” pathological type.

Metabolic Syndrome: the Influence of Adipokines on the L-Arginine-NO Synthase-Nitric Oxide Signaling Pathway

Metabolic syndrome includes the following symptoms: obesity, hyperlipidemia, hypertension, insulin resistance, and cardiovascular disease. The purpose of this review is to elucidate the role of adipokines in the regulation of the L-arginine-NO-synthas-NO signaling pathway in the pathogenesis of metabolic syndrome. The main questions raised in the review are: how adipokine secretion changes, how the level of their receptors is regulated, and which signaling pathways are involved in the transmission of adipokine signals when coupled to the L-arginine-NO-synthase-NO signaling cascade. Adipokines are peptide hormones that transmit a signal from adipose tissue to targets in the brain, blood vessels, liver, pancreas, muscles, and other tissues. Some adipokines have anti-inflammatory and insulin-sensitive effects: adiponectin, omentin, adipolin, chemerin, progranulin. Others have the negative inflammatory effect in the development ofmetabolic syndrome: visfatin, vaspin, apelin. Adipokines primarily regulate the expression and activity of endothelial NO-synthase. They either activate an enzyme involving 5-AMP protein kinase or Akt kinase, increasing its activity and synthesis of NO in the tissues of healthy patients: adiponectin, adipolin, omentin, or inhibit the activity of eNOS, which leads to a decrease in NO-synthase and suppression of mRNA bioavailability: vaspin, visfatin, apelin in metabolic syndrome, and a decrease in its activity leads to dissociation and endothelial dysfunction. It should be noted that the bioavailability of NO formed by NO-synthase is affected at many levels, including: the expression ofNO-synthase mRNA and its protein; the concentration of L-arginine; the level of cofactors of the reaction; and to detect the maximum activity of endothelial NO-synthase, dimerization of the enzyme is required, posttranslational modifications are important, in particular, phosphorylation of endothelial NO-synthase by serine 1177 with the participation of 5-AMP protein kinase, Akt kinase and other kinases. It should be noted that the participation of adiponectin, omentin, and kemerin in the regulation of the L-arginine-NO-synthase-NO cascade in metabolic syndrom opens up certain opportunities for the development of new approaches for the correction of disorders observed in this disease. The review analyzes the results of research searching in PubMed databases, starting from 2001 and up to 2020 using keywords and adipokine names, more than half of the references of the last 5 years.

Chronic periodontitis and ischemic heart disease: morphofunctional relation-ships

The relationship between periodontal diseases and cardiovascular pathology is actively being studied. The clinical significance of tissue markers of endothelial dysfunction in acute or chronic periodontitis needs to be clarified. Materials and methods. The results of the examination of 65 patients with chronic generalized periodontitis (CP), 35 patients with chronic coronary heart disease (CHD), and 35 patients with combined pathology including CHD and CP were presented. Clinical instrumental examination, assessment of the functional state of the endothelium, immunohistochemical, and morphometric studies were performed. Results. Patients with moderate CP were characterized by functional changes in the endothelium, decreased expression of the vasodilating factor (e-NO-synthase), and endothelial progenitor cells (CD34+cells) in the vascular wall. In patients with CHD without periodontitis, there was also a decrease in the expression and optical density of endothelial NO-synthase and endothelial progenitor cell in the periodontal vessels. Conclusion. Apparently, changes in the expression of endothelial NO-synthase and endothelial progenitor cells (CD34+cells) in the vascular wall are generalized, and the gum can serve as a promising material for the early assessment of endothelial dysfunction.

Changes in the asymmetric dimethylarginine and endothelial nitric oxide synthase levels in pathogenesis of experimental diabetic retinopathy

Endothelial dysfunction associated with impaired nitric oxide excretion plays an important role in the onset and progression of diabetic retinopathy. It has been proven that a decrease in the activity of endothelial NO-synthase (еNО-S), the inhibitor of which is asymmetric dimethylarginine (ADMA), plays an important role in this. Objective: to study the level of asymmetric dimethylarginine and endothelial nitric oxide synthase at different stages of development of diabetic retinopathy in the experiment. The study was conducted in Wistar white rats of 180-200 g weight. According to the tasks, the animals were separated into 2 groups as follows: group 1 – 60 intact animals, group 2 – 60 animals with simulated diabetic retinopathy without further correction. Type 2 diabetes mellitus and diabetic retinopathy were simulated through intraperitoneal administration of Streptozotocin (Sigma, USA) diluted in 0.1M citrate buffer with pH=4.5. Streptozotocin dose of 55 mg per kg of animal weight was divided into two administrations. The streptozotocin intake was preceded by a 28-day high-fat diet. Our study showed impaired endothelial function in diabetic retinopathy, as evidenced by an increased ADMA level (p<0.001). We have determined a stepwise increase of asymmetric dimethylarginine level in blood of rats with simulated pathology which is apparent in its highest at phase 3. Pathogenetic effect of increased ADMA on еNО-S activity was verified at all experimental stages, Impairment of physiological nitric oxide synthesis in simulated pathology has been proved as evidenced by reduced activity of endothelial NO-synthase yet on the 30th day with further negative dynamics up to the 180th day (p<0.001 compared with the intact group findings).

P6603The predictive role of T786C single nucleotide polymorphism in endothelial no-synthase gene in late left ventricular remodeling after ST-segment elevation myocardial infarction

Introduction Endothelial NO-synthase (eNOS) is constitutive enzyme, which is expressed in mature endothelial cells and promotes direct vascular dilatation. Single nucleotide polymorphism (SNP) of T786C in eNOS gene may influence on adverse cardiac remodeling after ST-elevation myocardial infarction (STEMI). Purpose To investigate possible associations between SNP T786C in eNOS gene and adverse cardiac remodeling after STEMI Methods 177 acute STEMI patients treated with primary and facilitate percutaneous coronary intervention that were admitted to intensive care unit of a Therapy National Institute were enrolled in the study. Anthropometry, cardiovascular risk assay, coronary angiography, echocardiography and biomarkers' measure were performed at baseline. The DNA extraction was performed with a commercial kit using real-time polymerase chain reaction PCR. All procedures performed in the study involving human participants were in accordance with the ethical standards and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and approved by the local ethics committee (Protocol No. 8, 29.08.2016). Written informed consent was obtained from each patient. Results There were correlations between 786CC polymorphism in eNOs gene and adverse cardiac remodeling (r=0.48; p=0.001), LDL cholesterol (r=0.32; p=0.012), type 2 diabetes mellitus (r=0.30; p=0.042), diastolic BP (r=−0.26; p=0.048), unstable angina prior to STEMI (r=0.25; p=0.047) and total quantity of complicated STEMI (r=0.23; p=0.042). Additionally, there were not significant relations between 786CC polymorphism in eNOs gene and multiple coronary vessel injury, STEMI localization, levels of circulating biomarkers of myocardial injury, and amount of damaged coronary arteries. Using univariate and multivariate regressive logistic analysis we found that 786CC genotype of eNOS was independent predictor for late adverse LV remodeling (β-coefficient = 1.57342; odds ratio = 4.8231; 95% confidence interval = 1.5349–15.1552; p=0.0071). Conclusions The polymorphism 786CC in eNOs gene was found as an independent predictor for late adverse cardiac remodeling after STEMI. Acknowledgement/Funding None