[The role of calcium sensitive and vitamin D receptors in the pathogenesis of sporadic multiple parathyroid gland disease].

BACKGROUND: Sporadic multiple parathyroid gland disease is » cases of primary hyperparathyroidism (PHPT). However, a single tactic for diagnosing and operating volume in patients with this variant of PHPT has not yet been developed. One of the possible directions in the search for pathogenetically substantiated methods of diagnosis and treatment is the study of the molecular genetic features of the disease and associated clinical and laboratory factors. AIM: To study the features of the expression of calcium sensitive (CaSR) and vitamin D (VDR) receptors on the surface of parathyroid cells in primary hyperparathyroidism with solitary and multiple lesions of the parathyroid glands, as well as its changes under the influence of a decrease in the filtration function of the kidneys. MATERIALS AND METHODS: In a single center observational prospective study with retrospective data collection, there were patients who during 2019-2021. operated on for PHPT, secondary hyperparathyroidism (SHPT) and all cases of tertiary hyperparathyroidism (THPT) operated during 2014-2021. The expression of CaSR, VDR and its relationship with the main laboratory parameters, the clinical variant of hyperparathyroidism, and the morphological substrate were studied. RESULTS: The study included 69 patients: 19 with multiple and 25 with solitary PTG near PHPT, 15 with SHPT, 10 with THPT. A statistically significant decrease in the frequency of detection of normal expression of CaSR and VDR receptors occurs in any morphological variant of hyperparathyroidism and is observed in 93-60% of drugs. A decrease in the normal expression of CaSR in hyperplasia is detected statistically significantly less frequently than in adenoma (p≤0.01). The median expression intensity in adenoma was 2.5 (2:3), in hyperplasia 3.5 (3-4) (p≤0.01). The difference in the molecular mechanisms of the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma (PHPT with solitary adenoma) or hyperplasia (SHPT and PHPT with multiple PTG lesions) is realized in the frequency of maintaining normal CaSR expression in the PTG tissue. These mechanisms are implemented at the local level, their variability does not change under the influence of RRT. A common molecular genetic mechanism for the development of hyperparathyroidism with a predominance of a morphological substrate in the form of adenoma or hyperplasia has been found to reduce the frequency of maintaining normal VDR expression in PTG (up to 7-13%), p<0.01. This mechanism is implemented at the local level, its variability changes under the influence of RRT, reaching statistically significant differences in patients with THPT. CONCLUSION: The study demonstrates the features of changes in the expression of CaSR and VDR in PHPT with multiple lesions of the parathyroid glands. The relationship between the expression of these receptors and the clinical variant of hyperparathyroidism, the morphological substrate, the main laboratory parameters, and renal function was shown.

Morphological Evaluation of Oxidative Phosphorylation System in Myocardial Infarction under Conditions of Modified Vascular Endothelial Growth Factor Concentration.

The relationship between vascular endothelium growth factor (VEGF) and cardiomyocyte oxidative phosphorylation level in experimental myocardial infarction, caused by diathermocoagulation of the periconical ventricular artery, was studied by immunofluorescent microscopy. Staining showed uneven distribution of cytochrome c in the mitochondria in the focus of myocardial infarction 2 h after the operation. After 24 h uneven staining of cardiomyocytes was found in the peri-infarction zone and no staining in the zone of myocardial infarction. This indicated a significant decrease in the level of redox enzymes. This picture persisted till day 14. Intraventricular injection of VEGF to animals led to a significant increase of the immunohistochemical reaction intensity, which reached the peak by day 7. The distribution of immunohistochemical reaction products under conditions of VEGF blocking was about the same as in spontaneous postinfarction reparative restitution. Our data indicated that increase of VEGF concentration in the myocardium maintained and stimulated oxidative phosphorylation in cardiomyocytes during the postinfarction period.

Endogenous progenitors as the source of cell material for ischemic damage repair in experimental myocardial infarction under conditions of changed concentration of vascular endothelial growth factor.

We studied the effect of VEGF-A in experimental myocardial infarction on attraction of progenitor cells into the regeneration zone. The appearance of CD34(+)CD45(+) cells known as low-differentiated progenitor cells was observed in the damaged myocardial tissue in the presence of a considerable excess of VEGF-A. These cells can act as precursors of mesenchymal tissues depending on the direction of differentiation.

Effect of endothelial growth factor on postinfarction remodeling of rat myocardium.

The reparative processes in the myocardium were studied during the postinfarction period after intracardiac injection of vascular endothelial growth factor. The cytoprotective and mitogenic effects of increased concentration of vascular endothelial growth factor on cardiomyocytes were revealed: viable muscle cells were present in the myocardial necrotic zone over 3 days, while cardiomyocytes in the periinfarction zone exhibited mitotic activity of within 7 days after infarction modeling. One of the main morphogenetic effects of high concentrations of vascular endothelial growth factor is stimulation of angiogenesis in all zones of the infarcted myocardium. On the other hand, injection of exogenous vascular endothelial growth factor stimulated collagen formation processes in the infarction zone (a 44% increase of the volume of collagen fibers) and formation of cardiosclerosis foci in neoangiogenesis zones in the intact myocardium, which is an unfavorable side effect of high concentrations of vascular endothelial growth factor.