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Loss of cardiomyocytes due to apoptotic or necrotic death is an important component of the pathogenesis of heart failure. Initiation of apoptosis by the mitochondrial pathway depends on the balance between proapoptotic and antiapoptotic factors, in particular, Bax and Bcl-2. Cardiomyocyte apoptosis in essential hypertension is studied in sufficient details. At the same time, apoptotic processes in the myocardium in diabetes mellitus alone and in combination with essential hypertension remain poorly understood. Here we studied the expression of Bax and Bcl-2 in the left ventricular cardiomyocytes of 38-week-old male Wistar-Kyoto rats and 38- and 57-week-old SHR rats with essential hypertension, diabetes mellitus, and a combination of these pathologies. Insulin-dependent diabetes mellitus was modelled by a single parenteral administration of streptozotocin in a dose 65 mg/kg. Expression of Bax and Bcl-2 was assessed by the immunohistochemical method. In essential hypertension and diabetes mellitus, the apoptotic processes in the ventricular myocardium were enhanced, as is seen from the increase in the content of the proapoptotic factor Bax and a decrease in the expression of the antiapoptotic factor Bcl-2. However, in case of combined pathology, Bax content increased less markedly, while the expression of antiapoptotic Bcl-2 was significantly increased.

Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.

A total of 100 women with early pregnancy loss were recruited and further classified into two subgroups: sporadic pregnancy loss and recurrent pregnancy loss; each subgroup consisted of 50 women. The control group included 56 women with normal pregnancies. Genotyping was performed by PCR with restriction fragment length polymorphism analysis. A statistically significant increase in the frequencies of TT genotype and T allele for DNMT3B rs2424913 polymorphism was found in the total patient group and in both patient subgroups in comparison with the control. Moreover, homozygous TT genotype was associated with increased risk of early pregnancy loss (both sporadic and recurrent). DNMT3B rs2424913 gene polymorphism in women can be used a marker of predisposition to early pregnancy loss and recurrent pregnancy loss.

The study included pregnant women aged 23-41 years with preeclampsia and gestation-associated arterial hypertension at weeks 27-40 and patients with essential arterial hypertension developing under conditions of the metabolic syndrome and without it. Frequency analysis of polymorphisms of the renin-angiotensin system genes (ACE, AGT, and AGTR1), ITGB3, FTO and their associations confirmed the syndrome nature of hypertensive disorders in pregnancy. The presence allele T of AGT gene and/or allele C of AGTR1 gene in the genotype of patients with preeclampsia was associated with higher BP and pressure load over 24 h. Allele D of ACE gene was also essential for BP parameters (pressure load) in patients with preeclampsia and gestation-associated arterial hypertension. Due to high genetic heterogeneity of the preeclampsia syndrome and genetic differences in the incidence of the studied gene polymorphisms in preeclampsia and gestation-associated arterial hypertension, no direct associations between these gestation disorders and polymorphic markers of the renin-angiotensin system genes can be established. However, polymorphisms of the renin-angiotensin system genes are essential for the 24-h dynamics of BP and pressure load under conditions of hypertensive disorders in pregnancy.

Restenosis remains the main complication after percutaneous coronary interventions in patients with coronary heart disease. The causes of its development include, in particular, genetic factors. We studied polymorphic loci of genes encoding endothelin-1 (EDN1 rs5370), endothelin-1 receptor (EDNRA rs5333), endothelin-converting enzyme (ECE1 rs1076669), and endothelial NO synthase (eNOS rs1549758, eNOS rs1799983, and eNOS rs2070244) in the context of in-stent restenosis development. It was found that the analyzed polymorphisms of the endothelin system genes were more significant for patients aged ≥ 65 years, while the polymorphic loci of the endothelial NO synthase gene (eNOS rs1799983 and eNOS rs1549758) were predominantly associated with time of in-stent restenosis. The obtained results can be useful for comprehensive assessment of the restenosis risk factors and the choice of optimal treatment for patients with coronary heart disease before elective surgical intervention.

In cardiomyocytes, high molecular ATP-dependent HSP70 and HSP90 play an important role in protecting the myocardium from abnormal proteins that appear, in particular, due to activation of oxidative stress. Molecular chaperone HSP60 is of particular importance for cardiomyocytes as it is responsible for assembly of mitochondrial matrix proteins. We studied the peculiarities of expression of HSP60 in left ventricular cardiomyocytes in hypertension, insulin-dependent diabetes mellitus, and their combination. The experiment was performed on 38-week-old male Wistar-Kyoto and SHR (spontaneously hypertensive) rats aged 38-57 weeks. Insulin-dependent diabetes mellitus was modeled by a single parenteral administration of 65 mg/kg streptozotocin. Expression of HSP60 in left ventricular cardiomyocytes was evaluated by immunohistochemical methods. It was found that hypertension, diabetes mellitus, and their combination are associated with a significant decrease in the content of HSP60 in left ventricular cardiomyocytes in comparison with the control. This finding can be considered as a pathogenetic mechanism of myocardial damage induced by hypertension and diabetes mellitus.

Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT, and ITGB3 genes were analyzed in patients with arterial hypertension coupled with metabolic syndrome (N=15) and compared with population data and corresponding parameters in patients with isolated hypertension (N=15). Increased frequency of genotype ID of ACE gene (hypertension predictor) was confirmed for both groups. In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in case of hypertension combined with metabolic syndrome, the frequency of genotypes A1166C and C1166C of the gene AGTR1 was higher in comparison with population data. Comparison of mutant allele frequencies in the two groups showed that at the 90% significance level allele T of the AGT gene was more frequent in hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the AGTR1 gene was more frequent in the group with isolated hypertension.

The expression of Bax protein, marker of intracellular pathway of apoptosis initiation, in viable left ventricular cardiomyocytes and morphological changes in the myocardium in acute pressure overload of the left ventricle were studied in experiment on male rabbits. The content of Bax protein in the cardiomyocyte cytoplasm decreased, this indicating that the mitochondrial pathway was not involved in the realization of the apoptotic program. This decrease was associated with manifest destructive changes in the left ventricular myocardium.

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

In SHR rats of different ages (22, 26, 30, 34, and 38 weeks), continuous 24-h telemetric monitoring of BP and HR was performed. The amplitude and power of oscillations of diastolic BP significantly decreased at the later stages of arterial hypertension (38 weeks), which was considered as a poor prognostic marker. We also observed a significant decrease in the mean daytime, nighttime, and maximum HR and mesor on weeks 30 and 34, but not on week 38, which can reflect triggering of the adaptive response followed by its exhaustion.

We studied the effect of phosphocreatine and ethylmethylhydroxypyridine succinate on the expression of Bax and Bcl-2 proteins in left-ventricular cardiomyocytes of spontaneously hypertensive rats (SHR). Both drugs have no effect on the expression of Bcl-2, but significantly reduce the level of Bax protein (phosphocreatine produces more pronounced effect). These data attest to an important role of energy deficit and oxidative stress in the induction of cardiomyocyte apoptosis in genetically determined arterial hypertension.

Numerous experiments on simulation of acute coronary failure in initially intact rabbits showed that under the same experimental conditions irreversible ventricular fibrillation developed in some animals and did not develop anothers. We hypothesize that the probability of fibrillation development was determined by the time of the day, during which acute coronary failure developed. The study was carried out on 2 groups of rabbits in winter in Moscow. In group 1, the failure was induced by ligation of the left descending coronary artery at the interface between its middle and lower thirds at 11.00-18.00 with 30-min intervals. In group 2, the microcirculatory status of the left-ventricular myocardium was studied by light microscopy and morphometry at 12.00 and 18.00. Induction of coronary failure during the period from 15.30 to 18.00 led to irreversible ventricular fibrillation and death in 100% cases. Modeling of the condition from 11.00 to 15.00 caused no ventricular fibrillation in 89% cases, and the animals survived. The area of left-ventricular myocardial capillaries at 12.00 virtually 2-fold surpassed that at 18.00. Presumably, the electrolyte balance and metabolic characteristics of the myocardium switch over to the nocturnal mode of functioning at 15.30 due to changes in blood filling of the myocardium. The appearance of an ischemic focus in the myocardium during this period inevitably leads to the development of irreversible ventricular fibrillation.