Antibodies against Angiotensin II Type 1 and Endothelin 1 Type A Receptors in Cardiovascular Pathologies

Angiotensin II receptor type 1 (AT1R) and endothelin-1 receptor type A (ETAR) are G-protein-coupled receptors (GPCRs) expressed on the surface of a great variety of cells: immune cells, vascular smooth cells, endothelial cells, and fibroblasts express ETAR and AT1R, which are activated by endothelin 1 (ET1) and angiotensin II (AngII), respectively. Certain autoantibodies are specific for these receptors and can regulate their function, thus being known as functional autoantibodies. The function of these antibodies is similar to that of natural ligands, and it involves not only vasoconstriction, but also the secretion of proinflammatory cytokines (such as interleukin-6 (IL6), IL8 and TNF-α), collagen production by fibroblasts, and reactive oxygen species (ROS) release by fibroblasts and neutrophils. The role of autoantibodies against AT1R and ETAR (AT1R-AAs and ETAR-AAs, respectively) is well described in the pathogenesis of many medical conditions (e.g., systemic sclerosis (SSc) and SSc-associated pulmonary hypertension, cystic fibrosis, and allograft dysfunction), but their implications in cardiovascular diseases are still unclear. This review summarizes the current evidence regarding the effects of AT1R-AAs and ETAR-AAs in cardiovascular pathologies, highlighting their roles in heart transplantation and mechanical circulatory support, preeclampsia, and acute coronary syndromes.

Indazole and its derivatives in cardiovascular diseases: Overview, current scenario and future perspectives

: Indazoles are a class of heterocyclic compounds with a bicyclic ring structure composed of a pyrazole ring and a benzene ring. Indazole-containing compounds with various functional groups have important pharmacological activities and can be used as structural motifs in designing novel drug molecules. Some of the indazole-containing molecules are approved by FDA and are already in the market. However, very few drugs with indazole rings have been developed against cardiovascular diseases. This review aims to summarize the structural and pharmacological functions of indazole derivatives which have shown efficacy against cardiovascular pathologies in experimental settings.

Investigation of the Effectiveness of Cortexin in the Treatment of Cardiac Arrhythmias in Children

In this article, a new look at cardiac rhythm and conduction disorders in children is outlined. These deviations, along with congenital malformations, have taken one of the first places in the structure of cardiovascular pathologies. This is one of the most serious problems that stands at the intersection of cardiology and pediatrics. The frequency of occurrence of severe forms of arrhythmias reaches 1:5000 of the child population, and life-threatening arrhythmias – 1:7000. Treatment of cardiac arrhythmias and conduction disorders is one of the most difficult sections of clinical pediatrics. There are medicinal and non-medicinal methods. According to experimental new data, nootropics, in particular the drug Cortexin, along with cardiotrophic drugs, form the basis of neuro-metabolic therapy and correction of children's arrhythmias.

The Role of Hyperhomocysteinemia in the Pathogenesis of Thromboocclusive Diseases

Homocysteine is a sulfur-containing non-proteinogenic amino acid that is an intermediate product of methionine metabolism. With excessive accumulation of homocysteine in the body, a state of hyperhomocysteinemia occurs, which has attracted the attention of doctors since the middle of the last century and received a serious impetus for research after the publication of data on the role of hyperhomocysteinemia in the pathogenesis of thromboocclusive diseases. To date, there are more than 7.5 thousand scientific papers devoted to the study of hyperhomocysteinemia, monothematic international conferences on clinical and therapeutic aspects of hypermonocysteinemia are held every year. In the Russian Federation, a detailed study of the role of homocysteine and its side effects in excess is of particular interest due to the prevalence of cardiovascular pathologies (according to statistics of the Ministry of Health of Russia-49.27% of deaths of Russians fall on this cohort of diseases). This is an important fact in Russian medicine, which deserves close attention from researchers and scientists.

Effect of Angiotensin-I Converting Enzyme Gene Insertion/Deletion Polymorphism on genome instability in children living in Russian Arctic

Main risks of arterial hypertension manifest in childhood. Children living in the Far North are especially susceptible to this. There is a need for an inexpensive, non-invasive and simple diagnosis of the risk of childhood pathologies. It was previously found that the genotype DD of the in/del polymorphic marker of the ACE gene is found in people at risk of developing cardiovascular pathologies. Buccal micronucleus cytome assay and genetic analysis were used in the work. In total, 77 schoolchildren from the city of Apatity, aged 15-17 years old, were examined. We have shown that carriers of the D allele have a tendency to an increase in the frequency of cells with micronuclei. In the case of homozygous I/I variant, the frequency of occurrence of cells with karyopycnosis is significantly higher than in carriers of allele D. Polymorphic marker in/del of the ACE gene is associated with apoptotic changes in the cells of the studied children. The in/del polymorphic marker of the ACE gene can be used as a prognostic marker of the processes of genome destabilization at the early stages of development of the human body.

The influence of geomagnetic and seismic parameters on mortality from cardiovascular pathologies in the Shamakhi Region of the Republic of Azerbaijan

Aim. Study of the dependence of mortality from CVD on helio-seismic indicators in the Shamakhi region of the Republic of Azerbaijan.Materials and methods. 352 case histories of patients who died in 2013 from various diseases were reviewed. The relationship was established between the number of deaths, their causes, distribution by sex and age with the magnitude of earthquakes, the depth of the epicenter and seismological activity by months. The data obtained were statistically processed using the Statistica 12.0 for Windows software package (Statsoft Inc., USA). To establish correlations, Pearson Chi-Square Tests was calculated, the results were considered reliable at p <0.05.Results. Statistically significant (p <0.001) more deaths were observed at the age of 80-89 years in men, and at the age of 70-79 years in women. Also, the relationship between mortality and the depth of the seismic process and the magnitude of the earthquake was established, in particular, the greatest number of deaths was observed at a depth of the seismic process <10 km and with a magnitude of 1.1-2.0 ml. In all months, the number of deaths was higher with a magnitude of 1.1-2.0 Ml. Statistically significant (p <0.005) was the fact that the nosology of the studied diseases was dependent on the age of the patients. Thus, a greater number of deaths in all age groups accounted for heart failure. A statistically significant (p <0.005) dependence of the depth of the seismic process on the month of death of patients was established, in particular, for all months, deaths coincided with the depth of the process less than 10 km. At the age of 40-70 years, a significantly greater number of deaths were from heart failure in men, and from 70 years and above in women.Conclusion. Thus, there is a close correlation between geomagnetic changes and mortality from CVD, which is realized in the form of an increase in the frequency of cases and deaths, and the number of these cases increases with the age of patients and changes in the magnitude and depth of the earthquake.

The role of influenza vaccination in the prevention of pulmonary and cardiovascular diseases

Influenza is an acute respiratory disease that causes annual epidemics and periodic pandemics with high mortality. It is characterized by the development of severe complications, the main of which are pulmonary and cardiovascular ones. The only effective method of preventing influenza, and therefore the influenza-associated complications, is vaccination, which is carried out annually on the basis of World Health Organization influenza vaccines composition recommendations. This article provides the review of the research data confirming the effective role of influenza vaccination in the prevention of pulmonary and cardiovascular pathologies (bibliography: 12 refs).

Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

: There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, stroke, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

Differential Expression of Long Noncoding RNAs in Patients with Coronary Artery Disease

Long noncoding RNAs (lncRNAs) constitute the largest class of noncoding RNAs and play significant roles in the development of cardiovascular pathologies. In the present study, we aimed to evaluate whether 4 candidate lncRNAs – MIAT, MEG3, MALAT1, and MCM3AP-AS1 – have distinct expression levels in patients with obstructive coronary artery disease (CAD) and reveal the diagnostic and therapeutic potentials of these lncRNAs for CAD. A total of 90 patients who subjected to coronary angiography were enrolled. Relative expression of lncRNAs were assayed using qRT-PCR methodology. As a result, <i>MIAT</i> was downregulated, while <i>MEG3</i> was upregulated in CAD patients. Receiver operating characteristic curves demonstrated that these lncRNAs have a high potential to provide sensitive and specific diagnosis of CAD. The calculated area under curve levels indicated that MIAT and MEG3 have high diagnostic value for detecting the presence of significant CAD. However, <i>MALAT1</i> and <i>MCM3AP-AS1</i> levels were not sufficiently reliable for CAD development in our cases. Here, we demonstrate that <i>MIAT</i> and <i>MEG3</i> were differentially expressed in our patients and might be promising biomarkers and therapeutic targets for CAD. These results indicate that <i>MIAT</i> and <i>MEG3</i> could play chief roles in CAD development.

Arginine:Glycine Amidinotransferase Is Essential for Creatine Supply in Mice During Chronic Hypoxia

Objective: Chronic hypoxia induces pulmonary and cardiovascular pathologies, including pulmonary hypertension (PH). L-arginine:glycine amidinotransferase (AGAT) is essential for homoarginine (hArg) and guanidinoacetate synthesis, the latter being converted to creatine by guanidinoacetate methyltransferase. Low hArg concentrations are associated with cardiovascular morbidity and predict mortality in patients with PH. We therefore aimed to investigate the survival and cardiac outcome of AGAT knockout (Agat−/−) mice under hypoxia and a possible rescue of the phenotype.Methods:Agat−/− mice and wild-type (WT) littermates were subjected to normoxia or normobaric hypoxia (10% oxygen) for 4 weeks. A subgroup of Agat−/− mice was supplemented with 1% creatine from weaning. Survival, hematocrit, blood lactate and glucose, heart weight-to-tibia length (HW/TL) ratio, hArg plasma concentration, and Agat and Gamt expression in lung, liver, and kidneys were evaluated.Results: After 6 h of hypoxia, blood lactate was lower in Agat−/−-mice as compared to normoxia (p &lt; 0.001). Agat−/− mice died within 2 days of hypoxia, whereas Agat−/− mice supplemented with creatine and WT mice survived until the end of the study. In WT mice, hematocrit (74 ± 4 vs. 55 ± 2%, mean ± SD, p &lt; 0.001) and HW/TL (9.9 ± 1.3 vs. 7.3 ± 0.7 mg/mm, p &lt; 0.01) were higher in hypoxia, while hArg plasma concentration (0.25 ± 0.06 vs. 0.38 ± 0.12 μmol/L, p &lt; 0.01) was lower. Agat and Gamt expressions were differentially downregulated by hypoxia in lung, liver, and kidneys.Conclusion:Agat and Gamt are downregulated in hypoxia. Agat−/− mice are nonviable in hypoxia. Creatine rescues the lethal phenotype, but it does not reduce right ventricular hypertrophy of Agat−/− mice in hypoxia.